Advertisement

Is Tactile Acuity Altered in People With Chronic Pain? A Systematic Review and Meta-analysis

Open AccessPublished:June 28, 2014DOI:https://doi.org/10.1016/j.jpain.2014.06.009

      Highlights

      • Tactile acuity is altered in people with non-neuropathic chronic pain conditions.
      • Tactile acuity is worse at the site of pain than at contralateral pain-free regions.
      • No significant associations between tactile acuity and pain intensity or duration were identified.

      Abstract

      Impaired tactile acuity in people with chronic pain conditions has been suggested to reflect altered cortical representation of the painful body part, and treatments that aim to improve tactile acuity in these conditions have shown clinical benefit. Whether abnormalities in tactile acuity are a consistent feature of chronic pain remains largely unknown. The aim of this review was to systematically evaluate the literature and use meta-analysis to establish whether tactile acuity is altered in people with chronic non-neuropathic pain. We systematically searched the literature for studies that investigated tactile acuity in people with chronic non-neuropathic pain and compared it to an appropriate control group. Sixteen studies, reporting data from 5 chronic pain conditions, were included. Data were available for 18 chronic pain populations (n = 484) and 15 control populations (n = 378). Our results suggest that tactile acuity is diminished in arthritis, complex regional pain syndrome, and chronic low back pain but not in burning mouth syndrome. The strength of the available evidence is weakened by somewhat inconsistent results and the high risk of bias observed in all of the included studies.

      Perspective

      This systematic review synthesizes the evidence for tactile acuity deficits in people with chronic non-neuropathic pain. The findings suggest that tactile acuity deficits may be characteristic of chronic pain. That tactile acuity training may benefit those with chronic pain disorders suggests that clinical trials may be warranted.

      Key words

      Tactile acuity refers to the precision with which we can sense touch,
      • Goldstein E.B.
      Tactile acuity.
      and this precision is thought to be impaired in some chronic pain conditions.
      • Moseley G.L.
      • Flor H.
      Targeting cortical representations in the treatment of chronic pain: A review.
      However, these impairments cannot be explained by deficits in tactile detection
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      or transmission
      • van Rijn M.A.
      • van Hilten J.J.
      • van Dijk J.G.
      Spatiotemporal integration of sensory stimuli in complex regional pain syndrome and dystonia.
      and thus are thought to reflect cortical changes, including a functional reorganization of the response profile of neurons in the primary somatosensory cortex (S1).
      • Flor H.
      Cortical reorganisation and chronic pain: Implications for rehabilitation.
      • Maihöfner C.
      • Neundörfer B.
      • Birklein F.
      • Handwerker H.O.
      Mislocalization of tactile stimulation in patients with complex regional pain syndrome.
      • Vartiainen N.V.
      • Kirveskari E.
      • Forss N.
      Central processing of tactile and nociceptive stimuli in complex regional pain syndrome.
      Discriminative ability is dependent on the integrity of S1
      • Duncan R.O.
      • Boynton G.M.
      Tactile hyperacuity thresholds correlate with finger maps in primary somatosensory cortex (S1).
      ; hence, in some chronically painful conditions, cortical reorganization appears to manifest as reduced tactile acuity at the affected body region. Whether tactile acuity deficits and cortical reorganization characterize all pain conditions remains largely unknown.
      This is important because treatments that aim to improve tactile acuity have shown clinical benefit in a number of chronic pain conditions.
      • Flor H.
      • Denke C.
      • Schaefer M.
      • Grüsser S.
      Effect of sensory discrimination training on cortical reorganisation and phantom limb pain.
      • Moseley G.L.
      • Zalucki N.M.
      • Wiech K.
      Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain.
      • Moseley G.L.
      • Wiech K.
      The effect of tactile discrimination training is enhanced when patients watch the reflected image of their unaffected limb during training.
      • Wand B.M.
      • O'Connell N.E.
      • Di Pietro F.
      • Bulsara M.
      Managing chronic nonspecific low back pain with a sensorimotor retraining approach: Exploratory multi-baseline study of 3 participants.
      • Wand B.M.
      • Abbaszadeh S.
      • Smith A.J.
      • Catley M.J.
      • Moseley G.L.
      Acupuncture applied as a sensory discrimination training tool decreases movement related pain in chronic low back pain patients more than acupuncture alone: A randomised cross-over experiment.
      There seems to be a growing view that tactile acuity deficit is a generic finding in chronic pain,
      • Moseley G.L.
      • Flor H.
      Targeting cortical representations in the treatment of chronic pain: A review.
      • Vartiainen N.V.
      • Kirveskari E.
      • Kallio-Laine K.
      • Kalso E.
      • Forss N.
      Cortical reorganization in primary somatosensory cortex in patients with unilateral chronic pain.
      irrespective of pathology or condition. If so, tactile acuity training might have a greater generic applicability than has currently been demonstrated. Despite this growing interest, there has been no attempt to systematically synthesize the evidence of tactile acuity deficits in chronic pain.
      We aimed to systematically evaluate the literature and use meta-analysis to establish whether tactile acuity is consistently altered in people with chronic pain. We focused our review on non-neuropathic pain conditions, as peripheral lesions of the somatosensory pathways may disrupt the transmission of tactile stimuli from the periphery and thus account for diminished acuity evident in neuropathic pain conditions.
      • Jerosch-Herold C.
      Assessment of sensibility after nerve injury and repair: A systematic review of evidence for validity, reliability and responsiveness of tests.
      • Rossini P.
      • Martino G.
      • Narici L.
      • Pasquarelli A.
      • Peresson M.
      • Pizzella V.
      • Tecchio F.
      • Torrioli G.
      • Romani G.
      Short-term brain “plasticity” in humans: Transient finger representation changes in sensory cortex somatotopy following ischemic anesthesia.
      • Tecchio F.
      • Padua L.
      • Aprile I.
      • Rossini P.M.
      Carpal tunnel syndrome modifies sensory hand cortical somatotopy: A MEG study.
      Primarily, we sought to determine whether tactile acuity is altered at the site of pain and/or at regions remote from the site of pain. Our secondary aims were to determine whether deficits in tactile acuity relate to pain intensity or to the duration of pain.

      Methods

      A systematic review of the peer-reviewed scientific literature was undertaken to locate studies that reported tactile acuity data for people with chronic pain. A review protocol was designed a priori in accord with the Cochrane Handbook for Systematic Reviews

      Higgins JPT, Green S (eds): Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available at: http://www.cochrane-handbook.org. Accessed December 2013

      and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement.
      guidelines.

      Data Sources

      Candidate studies were identified in June 2013 via a computer search of online bibliographic databases (AMED, CINAHL, Cochrane Library, Embase, Medline, PsycINFO, Scopus, and Web of Science). Each database was searched separately from its inception, and the search string proximity operators and expanders were appropriately customized for each database (see Supplemental Information for the Medline search string). No restrictions were placed on the language of the articles or the publication date. All duplicates were removed.

      Study Selection

      All titles and abstracts (where available) were initially screened independently by 2 reviewers (M.J.C. and C.B.) to identify eligible articles. The full-text articles of the potentially relevant studies were retrieved and reviewed independently by the same pair of reviewers. Study eligibility was compared at each stage and any discrepancies were resolved by discussion between the 2 reviewers; if agreement could not be reached, a third reviewer (N.E.O.) would arbitrate.
      Studies were included if they potentially reported tactile acuity data on a population of chronic pain patients. Studies were excluded if tactile acuity data were not reported for a definable chronic pain group (pain persisting for 3 months or longer
      ); control data (from a separate control group or the unaffected side) were not reported; the sample included people diagnosed with a central neurologic disorder (eg, stroke, multiple sclerosis), demonstrable nerve injuries (includes nerve compression injuries diagnosed electrophysiologically), or repairs; or the presented data were duplicated from an existing study. The reference lists of all relevant studies were examined and cross-referenced to identify additional studies.

      Outcome Measures

      Measures of tactile acuity were the primary outcomes of interest in this review. Comparable measures included tests of 2-point discrimination, tactile spatial localization, and grating orientation tasks. Comparisons of graphesthesia were not considered because they are task performance based rather than distance based. Secondary outcome measures were pain duration and pain intensity (eg, visual analog scale, numerical rating scale [NRS], McGill Pain Questionnaire [MPQ]).

      Risk of Bias Assessment and Data Extraction

      Two reviewers (M.J.C. and C.B.) independently assessed the included studies for risk of bias. The form used was based on the STROBE statement
      • von Elm E.
      • Altman D.G.
      • Egger M.
      • Pocock S.J.
      • Gotzsche P.C.
      • Vanderbroucke J.P.
      The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies.
      and relevant items for case-control study designs from the Cochrane Collaboration's tool for assessing bias (see Supplemental Information).
      • Berryman C.
      • Stanton T.R.
      • Bowering K.J.
      • Tabor A.
      • McFarlane A.
      • Moseley G.L.
      Evidence for working memory deficits in chronic pain: A systematic review and meta-analysis.

      Higgins JPT, Green S (eds): Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available at: http://www.cochrane-handbook.org. Accessed December 2013

      Data extraction was completed independently by the 2 reviewers (M.J.C. and C.B.) using a customized data extraction sheet. The data extraction sheet was piloted on several studies before the commencement of the search. The following descriptive data were extracted from each included study: age, gender, sample size, chronic condition, region of pain, region assessed, pain intensity, pain duration. Extracted outcome measures were mean (standard deviation [SD]) tactile acuity, assessment protocol, assessment tool, body region of pain (for the patient group), body region assessed, and any association data comparing tactile acuity and pain intensity and/or pain duration. Reviewer differences were resolved through discussion; if an agreement could not be reached, a third reviewer (N.E.O) would arbitrate.
      The authors of the included studies were contacted to clarify the details of their study and to request raw data, which included measures of pain intensity and/or pain duration. Raw data were entered into SPSS Statistics (v21.0.0.0; IBM Corporation, New York, NY). Tactile acuity data were entered in millimeters, and pain duration data were entered in months.

      Data Analysis and Synthesis

      Comparing Tactile Acuity Between People With Chronic Pain and Controls

      Studies that compared the tactile acuity of people with chronic pain to the tactile acuity of controls were first split into 2 groups: studies that compared tactile acuity assessed at the painful region and studies that compared the tactile acuity at a site remote from the painful region. The study data were then subgrouped by chronic pain condition (determined a priori) for comparison. Quantitative analysis was conducted using Review manager software (Revman v5.2.5; The Nordic Cochrane Centre, Copenhagen, Denmark). Studies were excluded from the quantitative analysis if they did not report sufficient data and the necessary data could not be obtained from the authors. When possible, mean and SD values were calculated from raw data. To simplify the comparison, in studies that included raw data for bilateral pain conditions, the mean (SD) of the left and right sides was compared with the control data. In instances where the same study reported several results on the same sample, the weighting was adjusted by dividing the sample size by the number of regions presented for that subgroup. Studies were pooled by the inverse variance method with a random effects model using the standardized mean difference (SMD) as the measure of effect size (Hedge's g). SMD was used instead of the weighted mean difference to better account for the predicted variation in acuity levels between studies of different body regions. Effect estimates were interpreted as small (.2), moderate (.5), or large (>.80).9 To further aid the interpretation of the pooled effect sizes, the SMD of subgroups in which all assessments were conducted at skin regions of comparable receptive field densities were back-transformed to a mean difference in millimeters using the averaged (mean) SD from the control data. The mean difference was then expressed as a percentage of the control group tactile acuity. As this calculation uses the averaged SD, taken from studies that used differing protocols and assessment tools, the results should be considered an estimate.
      All forest plots were visually inspected and a sensitivity analysis was conducted if the effect estimate of a data set within a subgroup appeared substantially different from the other studies and thus may have influenced the pooled effect estimate.

      Comparing Tactile Acuity Between the Affected and Unaffected Sides of People With Unilateral Chronic Pain Conditions

      The tactile acuity of the affected and unaffected sides of people with unilateral chronic pain was compared. The study data were grouped by chronic pain condition and the analysis was conducted as for the aforementioned comparisons.

      Relationship Between Tactile Acuity and Pain Intensity and Duration

      Correlational data were extracted and presented. For studies in which raw data were available, correlation coefficients were calculated. Furthermore, a Spearman's correlation coefficient (rS) was calculated to estimate the overall relationship between tactile acuity and the intensity and duration of pain. Tactile acuity data were transformed into z-scores and pooled. Average pain intensity data were converted to the most commonly used scale (eg, 0–100 mm visual analog scale converted to 0–10 NRS), and the pain duration data were converted into months. Scatterplots displaying the relationship between tactile acuity and pain intensity and/or duration were generated using MYSTAT 12 for Windows (v12.02.00; SYSTAT Software Inc, Chicago, IL).

      Results

      Fig 1 outlines the results of the systematic review process (PRISMA flow chart). The initial search identified 2,621 studies. Of these, 2,531 were excluded in the initial screening of titles and abstracts. A further 74 were excluded following the review of the full text. The most common reason for exclusion was a lack of control data (unaffected side or independent healthy sample). Other common reasons for exclusion included peripheral nerve injuries, central nervous system disorders, or secondary analyses. No additional studies were identified from searching the reference lists of the eligible studies. In total, 16 studies—reporting data for 484 people with chronic pain and 378 control individuals—were included in the analysis.
      Figure thumbnail gr1
      Figure 1Flow diagram describing the review and screening process.
      All the authors of the 16 included studies were contacted for their raw data and to clarify some details of their studies that were not clear from the study report. The authors of 5 studies
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      • Grushka M.
      • Sessle B.J.
      • Howley T.P.
      Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      • Seltzer S.F.
      • Seltzer J.L.
      Tactual sensitivity of chronic pain patients to non-painful stimuli.
      • Seltzer S.F.
      • Yarczower M.
      • Woo R.
      • Seltzer J.L.
      Laterality and modality-specific effects of chronic pain.
      did not respond. The raw data for 3 studies were unobtainable because they had been destroyed
      • Peters M.L.
      • Schmidt A.J.M.
      A comparison of two-point discrimination threshold of tactual, non-painful stimuli between chronic low back pain patients and controls.
      or the authors reported that they were currently inaccessible.
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      Raw data were obtained for the remaining 8 studies.
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      • Luomajoki H.
      • Moseley G.L.
      Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.

      Study Characteristics

      Table 1 summarizes the study characteristics of the 16 included studies. Fifteen studies compared people with chronic pain to control individuals, including 5 studies
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      that also compared tactile acuity at the site of pain to that of the contralateral unaffected region. One study
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      only compared tactile acuity at the site of pain to that of the contralateral unaffected region and did not include a healthy control group. Data were available for 18 chronic pain samples, representing 5 specific chronic pain conditions (burning mouth syndrome n = 72, complex regional pain syndrome [CRPS] n = 97, chronic low back pain [CLBP] n = 127, osteoarthritis [OA] n = 121, rheumatoid arthritis [RA] n = 28), some unspecified chronic pain patients (n = 39), and 16 control samples (n = 378).
      Table 1Summary of Study Demographics
      StudyYear of PublicationChronic Pain ConditionRegion of PainRegion AssessedChronic Pain ParticipantsControl Participants
      Sample Size (Females)Age (Mean [SD])Pain Intensity
      Current pain intensity unless specified.
      (Mean [SD])
      Pain Duration (mo)Control TypeSample Size (Females)Age (Mean [SD])Raw Data Provided
      Ayhan et al
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      2011RA and OAHandsIndex fingerRA: 28 (28); OA: 43 (43)RA: 55.9 (9.5); OA: 58.9 (4.8)RA: 4.3 (1.2)RA: 117.1 (102.5); OA: 34.0 (12.0)Healthy sample39 (39)56.6 (5.8)
      Batterman
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      1966Chronic arthritis?Forearm58 (?)???Healthy sample27 (12)?
      Grushka et al
      • Grushka M.
      • Sessle B.J.
      • Howley T.P.
      Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
      1987Burning mouth syndromeMouth (unspecified)Tongue, palate, lip, cheek72 (61)Males: 45.5 (11.2); females: 59.0 (9.9)MPQ: mean 2.339.6 (36.0)Healthy sample43 (36)Males: 47.7 (13.8); females 58.1 (7.5)
      Lewis and Schweinhardt
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      2012Unilateral CRPSUpper limbIndex finger22 (15)50.6 (10.6)NPSI: 20.34 (12.5)37.2 (53.7)Healthy sample and unaffected side22 (?)43.0 (14.2)
      Luomajoki and Moseley
      • Luomajoki H.
      • Moseley G.L.
      Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls.
      2011CLBPT10–L5L1 and iliac crest45 (25)43.0 (15.0)??Healthy sample45 (25)41.0 (10.0)
      Maihöfner and DeCol
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      2007Unilateral CRPSUpper limbIndex finger12 (10)50.9 (3.9)0–100 NRS: 40.8 (5.6)

      MPQ-PRI: 22.2 (4.9)
      5.4 (1.5)Healthy sample and unaffected side12 (8)48.2 (3.5)
      Moseley
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      2008CLBPLumbar regionT4–gluteal folds6 (3)43.8 (11.1)100 mm VAS: 47.2 (12.5)52.2 (36.1)Upper limb pain patients10 (5)42.3 (11.3)
      Calculated from raw data (not reported in manuscript).
      Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      2011Unilateral CRPSUpper limbIndex finger30 (19)50.9 (12.3)MPQ: 24.6 (15.0)

      0–100 NRS: 39.2 (16.3)
      16.8 (12.6)Healthy sample and unaffected side??
      Peters and Schmidt
      • Peters M.L.
      • Schmidt A.J.M.
      A comparison of two-point discrimination threshold of tactual, non-painful stimuli between chronic low back pain patients and controls.
      1991CLBPBack (unspecified)Lateral forearm20 (10)43.6 (range 21–55)?103.2 (12–360)Healthy sample20 (10)43.6 (range 20–60)
      Pleger et al
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      2006Unilateral CRPSHand (including digits)Index finger17 (10)40.1 (9.5)NRS: 5.4 (2.1) current; 4.0 (1.4) sustained17.1 (20.6)Healthy sample and unaffected side17 (10)40.2 (10.0)
      Reiswich et al
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      2012CRPSUpper limb (unspecified)Index finger16 (10)51.8 (10.8)NRS: 3.0 (1.1)12.4 (12.7)Healthy sample47 (27)43.9 (15.8)
      Saeidian et al
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      2011Lumbosacral radiculopathyLow back (unspecified)L4–S120 (20)Range 40–58VAS (unspecified): 8.5 (1.7)?Unaffected sideNANA
      Seltzer and Seltzer
      • Seltzer S.F.
      • Seltzer J.L.
      Tactual sensitivity of chronic pain patients to non-painful stimuli.
      1986Chronic painLow back, neck, arm, leg, generalizedLateral forearm19 (?)???Healthy sample19 (?)?
      Seltzer et al
      • Seltzer S.F.
      • Yarczower M.
      • Woo R.
      • Seltzer J.L.
      Laterality and modality-specific effects of chronic pain.
      1992Unspecified chronic pain?Lateral forearm20 (?)???Healthy sample20 (?)?
      Stanton et al
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      2013OA and CLBPKnee; low back (unspecified)Medial and lateral knee; L1–iliac crest20 (14) OA knee; 17 (14) back68 (9); 45 (15)100 mm VAS: 21.9 (25.5); 34.1 (22.4)90.5 (168.1); 30.9 (72.1)Healthy sample and unaffected side20 (12) hand controls; 18 (12) back controls37 (16); 41 (11)
      Wand et al
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      2010CLBPLow back (unspecified)Transverse process at L319 (11)41 (12.5)NRS: 3.2 (3.0)108 (117.6)Healthy sample19 (14)34 (12.1)
      Abbreviations: NPSI, Neuropathic Pain Symptom Inventory; VAS, visual analog scale.
      NOTE. ?, not reported.
      Current pain intensity unless specified.
      Calculated from raw data (not reported in manuscript).
      All of the included studies used the 2-point discrimination threshold (TPDT) as a measure of tactile acuity. Eleven studies
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      • Grushka M.
      • Sessle B.J.
      • Howley T.P.
      Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Luomajoki H.
      • Moseley G.L.
      Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls.
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Peters M.L.
      • Schmidt A.J.M.
      A comparison of two-point discrimination threshold of tactual, non-painful stimuli between chronic low back pain patients and controls.
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      • Seltzer S.F.
      • Seltzer J.L.
      Tactual sensitivity of chronic pain patients to non-painful stimuli.
      • Seltzer S.F.
      • Yarczower M.
      • Woo R.
      • Seltzer J.L.
      Laterality and modality-specific effects of chronic pain.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      used commercially available clinically applicable tools, whereas 5 studies
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      used custom-made assessment tools. Two studies
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      failed to clarify (or adequately reference) their protocols sufficiently for replication; attempts to contact these authors were unsuccessful. Whether tactile acuity was assessed directly within the painful region was unclear.
      Six studies used recognized diagnostic criteria. Maihöfner and DeCol,
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      Pleger et al,
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      and Lewis and Schweinhardt
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      used the International Association for the Study of Pain Diagnostic Criteria for CRPS.
      • Merskey H.
      • Bogduk N.
      Classification of Chronic Pain, IASP Task Force on Taxonomy.
      Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      and Reiswich et al
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      used the Budapest Research Criteria
      • Harden R.N.
      • Bruehl S.P.
      Diagnosis of complex regional pain syndrome: Signs, symptoms, and new empirically derived diagnostic criteria.
      for CRPS. Stanton et al
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      used the Altman et al
      • Altman R.
      • Asch E.
      • Bloch D.
      • Bole G.
      • Borenstein D.
      • Brandt K.
      • Christy W.
      • Cooke T.D.
      • Greenwald R.
      • Hochberg M.
      Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee.
      criteria to diagnose OA.

      Risk of Bias

      Table 2 displays the results of the risk of bias assessment. The risk of bias was high across multiple domains in all of the included studies. Although most studies reported the sampling method (81%), all but 2 studies used samples of convenience, with only Moseley
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      recruiting consecutive patients and Saeidian et al
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      using an undisclosed random sampling technique. Only 6 studies recruited participants using recognized diagnosis criteria (38%) and of these, only 4 of the 6 excluded controls on the same basis. Although most studies reported the protocol used to assess tactile acuity, none of the studies reported or cited reliability indices for their protocols. Of the 15 studies that compared people with chronic pain to control individuals, only 8 (53%) attempted to age-match their control group. Only 3 of the included studies (19%) used appropriately sized samples, and none of the studies justified the size of their samples. Critically, all but 1 study
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      (94%) failed to blind the assessor to the group.
      Table 2Risk of Bias in Included Studies
      Selection BiasDetection BiasReporting BiasPerformance Bias
      Replicable Sampling MethodRepresentative of CasesRecognized Diagnosis CriteriaDiagnosis ControlsAppropriate Sample SizeAge Matched ControlsNo Missing DataMissing Data DescribedBlinded AssessorAssessment Protocol ReportedReliable Assessment
      Ayhan et al
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      ???
      Batterman
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      ???
      Grushka et al
      • Grushka M.
      • Sessle B.J.
      • Howley T.P.
      Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
      ???
      Lewis and Schweinhardt
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      ?NA?
      Luomajoki and Moseley
      • Luomajoki H.
      • Moseley G.L.
      Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls.
      ?
      Maihöfner and DeCol
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      NA?
      Moseley
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      Peters and Schmidt
      • Peters M.L.
      • Schmidt A.J.M.
      A comparison of two-point discrimination threshold of tactual, non-painful stimuli between chronic low back pain patients and controls.
      ?
      Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      ?NA
      Pleger et al
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      ?
      Reiswich et al
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      ?NA?
      Saeidian et al
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      NA
      Seltzer and Seltzer
      • Seltzer S.F.
      • Seltzer J.L.
      Tactual sensitivity of chronic pain patients to non-painful stimuli.
      ??
      Seltzer et al
      • Seltzer S.F.
      • Yarczower M.
      • Woo R.
      • Seltzer J.L.
      Laterality and modality-specific effects of chronic pain.
      ???
      Stanton et al
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      ?NA?
      Wand et al
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      NOTE. ✓, yes (low risk of bias); ✗, no (high risk of bias); ?, unclear; NA, criterion not applicable.

      Outcomes

      Is Tactile Acuity Altered at the Painful Region in People With Chronic Pain?

      Eleven studies
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      • Bowering K.J.
      • O'Connell N.E.
      • Tabor A.
      • Catley M.J.
      • Leake H.B.
      • Moseley G.L.
      • Stanton T.R.
      The effects of graded motor imagery and its components on chronic pain: A systematic review and meta-analysis.
      • Grushka M.
      • Sessle B.J.
      • Howley T.P.
      Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Luomajoki H.
      • Moseley G.L.
      Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      assessed tactile acuity at the painful region and compared it with the same region in controls. The forest plot shown in Fig 2 compares the tactile acuity of people with chronic pain (n = 296) to that of controls (n = 341). The pooled results of all comparisons suggest that TPDTs are larger at the site of pain in people with chronic pain than they are in controls. A large, significant effect estimate of 1.02 (95% confidence interval [CI]: .59 to 1.46, P < .0001) in favor of worse tactile acuity in people with chronic pain was noted. However, heterogeneity was high (I2 = 81.8%, P = .0009) and there were apparent differences between diagnostic subgroups.
      Figure thumbnail gr2
      Figure 2Forest plot comparing tactile acuity, assessed at the painful region, of people with chronic pain and healthy pain-free controls. All included studies used the TPDT as a measure of acuity; hence, larger thresholds indicate worse acuity. Abbreviations: IV, inverse variance; CI, confidence interval. Note: †, bilateral limb pain (mean TPDT); ‡, unilateral limb pain (affected side TPDT); *, sample size reduced to adjust study weighting; •, calculated from raw data.

      Arthritic Pain

      Two studies
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      compared the tactile acuity of people with chronic arthritic pain to that of controls. Despite differences in protocols and assessment tools used, heterogeneity within this subgroup was not statistically significant (P = .13). The pooled results of 5 comparisons suggest that TPDTs are larger at the site of pain than they are in controls, a large, significant effect estimate of 1.48 (95% CI: .77 to 2.19, n = 24) in favor of worse tactile acuity in people with arthritis. However, the results appear inconsistent, with a difference in acuity observed at the knee in people with knee OA but no differences in acuity at the fingertip in people with hand OA and RA.

      Burning Mouth Syndrome

      One study
      • Grushka M.
      • Sessle B.J.
      • Howley T.P.
      Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
      compared the tactile acuity of people with burning mouth syndrome to that of controls. The pooled results of 8 oral regions assessed suggest that TPDTs are not altered in people with burning mouth syndrome (effect estimate .02, 95% CI: −.37 to .41, with no heterogeneity). This equates to a difference of .1 mm (95% CI: −1.4 to 1.6 mm), or a percentage difference of 0% (95% CI: −18% to 19%) between the people with burning mouth syndrome and controls.

      CRPS

      Five studies
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      compared the tactile acuity of people with CRPS to that of controls. The pooled results of 5 comparisons suggest that TPDTs are larger at the site of pain in people with CRPS than they are in controls; a large, significant effect estimate of 2.34 (95% CI: .86 to 3.83, P = .002) in favor of worse tactile acuity in people with CRPS was noted. This equates to a difference of 1.1 mm (95% CI: .4 mm to 1.8 mm), or a percentage difference of 47% (95% CI: 17% to 76%) between the people with CRPS and controls. However, substantial heterogeneity was observed for this comparison (I2 = 94%, P < .00001) even though all of the included studies demonstrated statistically significant differences in TPDTs. The results of Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      had much lower variance than the other studies, which may have contributed to their remarkably large effect size (6.48, 95% CI: 5.18 to 7.79; see Appendix for further discussion of the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      study). Considering this discrepancy and several anomalies found in their data, sensitivity analyses with the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      data excluded were undertaken (see Supplementary Fig 1). The pooled results of the remaining 4 studies suggest that TPDTs are larger at the site of pain in people with CRPS (effect estimate 1.35, 95% CI: .69 to 2.01, P < .0001), and although heterogeneity remained significant, it was lower with the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      study removed (I2 = 69%, P = .02). This equates to a difference of .8 mm (95% CI: .4 mm to 1.1 mm), or a percentage difference of 31% (95% CI: 16% to 47%) between the people with CRPS and controls.

      CLBP

      Four studies
      • Luomajoki H.
      • Moseley G.L.
      Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls.
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      compared the tactile acuity of people with CLBP to that of controls. The pooled results of 5 comparisons suggest that TPDTs are larger in people with CLBP; a large, significant effect estimate of 1.14 (95% CI: .54 to 1.74, P = .0002) in favor of worse tactile acuity in people with CLBP was noted. This equates to a difference of 11.7 mm (95% CI: 5.5 mm to 17.8 mm), or a percentage difference of 26% (95% CI: 12% to 39%) between the people with CLBP and controls. Substantial heterogeneity for this comparison was observed (I2 = 69%, P = .01).

      Is Tactile Acuity Altered in Regions Remote From the Region of Pain, in People With Chronic Pain?

      Eight studies
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Peters M.L.
      • Schmidt A.J.M.
      A comparison of two-point discrimination threshold of tactual, non-painful stimuli between chronic low back pain patients and controls.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Seltzer S.F.
      • Seltzer J.L.
      Tactual sensitivity of chronic pain patients to non-painful stimuli.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      assessed tactile acuity at a site remote from the region of pain. The remote locations where tactile acuity was assessed are described in the forest plot in Fig 3. The plot compares the tactile acuity of people with chronic pain (n = 194) to that of controls (n = 165). The pooled results of 8 comparisons suggest that TPDTs are larger at regions remote from the site of pain in people with chronic pain in comparison with healthy pain-free people; a moderate, significant effect estimate of .64 (95% CI: .26 to 1.02) in favor of worse tactile acuity in people with chronic pain was noted. Again, tactile acuity was not consistently altered in all of the included conditions, and the differences between subgroups was substantial (I2 = 83.6%, P = .0004).
      Figure thumbnail gr3
      Figure 3Forest plot comparing tactile acuity, assessed at a location remote from the painful region, of people with chronic pain and healthy pain-free controls. All included studies used the TPDT as a measure of acuity; hence, larger thresholds indicate worse acuity. Abbreviations: IV, inverse variance; CI, confidence interval. Note: ‡, unilateral limb pain (unaffected side TPDT); •, calculated from raw data.

      Arthritic Pain

      Two studies
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      compared the tactile acuity of people with chronic arthritic pain to that of controls. The pooled results of 2 comparisons suggest that TPDTs are larger at regions remote from the site of pain in people with chronic arthritic pain; a large, significant effect estimate of 1.40 (95% CI: .99 to 1.82, P < .00001) in favor of worse tactile acuity in people with arthritis was noted. Despite differing protocols (ie, Batterman
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      assessed the TPDT with a custom-built air jet apparatus) and differing clinical presentations (ie, Batterman
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      did not report which joints were affected), heterogeneity was not detected (I2 = 0%, P = .94).

      CRPS

      Four studies
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      compared the tactile acuity of people with CRPS to that of controls. The pooled results of 4 comparisons suggest that TPDTs are larger at regions remote from the site of pain in people with CRPS; a small, significant effect estimate of .33 (95% CI: .01 to .64, P = .04) in favor of worse tactile acuity in people with CRPS was noted. This equates to a difference of .13 mm (95% CI: 0 mm to .24 mm), or a percentage difference of 5% (95% CI: 0% to 10%) between the people with CRPS and controls. Heterogeneity was not detected (I2 = 0%, P = .56) but a sensitivity analysis was conducted with the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      study excluded (see Supplementary Fig 2). The pooled results of the remaining 3 studies suggest that TPDTs are not altered at regions remote from the site of pain in people with CRPS (95% CI: −.17 to .61, P = .28), which suggests that the significant pooled effect was probably carried by the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      data.

      CLBP

      One study
      • Peters M.L.
      • Schmidt A.J.M.
      A comparison of two-point discrimination threshold of tactual, non-painful stimuli between chronic low back pain patients and controls.
      compared the tactile acuity of people with CLBP to that of controls. The results suggest that TPDTs are not altered at regions remote from the site of pain in people with CLBP (95% CI: −.26 to .88).

      Nonspecific Chronic Pain

      One study
      • Seltzer S.F.
      • Seltzer J.L.
      Tactual sensitivity of chronic pain patients to non-painful stimuli.
      compared TPDTs at the forearm in people with chronic pain in various body regions to the forearm TPDTs of controls. The results suggested that TPDTs at the forearm are larger in people with chronic pain; a moderate, significant effect estimate of .77 (95% CI: .09 to 1.45, P = .03) in favor of worse tactile acuity in people with chronic pain was noted. This equates to a difference of 5.7 mm (95% CI: .7 mm to 10.7 mm), or a percentage difference of 19% (95% CI: 2% to 35%) between the people with nonspecific chronic pain and controls. However, these data included people with pain in the arm and generalized pain.
      An additional study not included in the overall analysis
      • Seltzer S.F.
      • Yarczower M.
      • Woo R.
      • Seltzer J.L.
      Laterality and modality-specific effects of chronic pain.
      compared TPDTs at the forearm in patients with unspecified chronic pain (ie, patient condition was not reported) to the forearm TPDTs of controls. They noted a significant difference (t[12] = 2.78, P < .02), but insufficient data were reported for its inclusion in the meta-analysis.

      Comparing Tactile Acuity of the Affected and Unaffected Sides of People With Chronic Pain

      Six studies
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Dinse H.R.
      • Ragert P.
      • Schwenkreis P.
      • Malin J.P.
      • Tegenthoff M.
      Shifts in cortical representations predict human discrimination improvement.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      measured tactile acuity in people with unilateral chronic pain (n = 118). The forest plot shown in Fig 4 compares tactile acuity at the region of pain with the contralateral unaffected region. The overall pooled results of 8 comparisons suggest that TPDTs are larger at the site of pain in comparison with the contralateral unaffected region; a large, significant effect estimate of 1.95 (95% CI: .87 to 3.03) in favor of worse tactile acuity at the site of pain was noted. Once again, tactile acuity was not consistently altered in all of the included conditions, and the differences between subgroups was substantial (I2 = 74.4%, P = .02).
      Figure thumbnail gr4
      Figure 4Forest plot comparing the tactile acuity of the painful region to the tactile acuity of the contralateral unaffected region in people with chronic pain. All included studies used the TPDT as a measure of acuity; hence, larger thresholds indicate worse acuity. Abbreviations: IV, inverse variance; CI, confidence interval. Note: *, sample size reduced and rounded to nearest whole number to adjust study weighting; •, calculated from raw data.

      Arthritic Pain

      One study
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      compared the tactile acuity of the affected and unaffected knees of people with chronic knee OA. The results suggest that the TPDT of the affected side is not altered in comparison with the unaffected side (95% CI: −.26 to 1.14).

      CRPS

      Four studies
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      compared the tactile acuity of the affected and unaffected limbs of people with CRPS. The pooled results of 4 comparisons suggest that TPDTs are larger at the site of pain in comparison with the contralateral unaffected region; a large, significant effect estimate of 2.39 (95% CI: .48 to 4.30) in favor of worse tactile acuity at the site of pain was noted. This equates to a difference of 1.2 mm (95% CI: .2 mm to 2.2 mm), or a percentage difference of 47% (95% CI: 10% to 87%) between the affected and unaffected sides. As noted above, substantial heterogeneity was observed for this comparison (I2 = 95%, P < .00001), probably because of the results of the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      study, which had an effect size 3.5 times the pooled estimate. A sensitivity analysis was conducted with the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      data excluded (see Supplementary Fig 3). The overall pooled results of the remaining 3 comparisons suggest that TPDTs are larger at the site of pain in comparison with the contralateral unaffected region (effect estimate 1.22, 95% CI: .43 to 2.02). This equates to a difference of .8 mm (95% CI: .3 mm to 1.2 mm), or a percentage difference of 29% (95% CI: 10% to 46%) between the affected and unaffected sides.

      CLBP

      One study
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      compared the tactile acuity of the affected and unaffected sides of people with unilateral CLBP. The pooled results of 3 comparisons suggest that TPDTs are larger at the site of pain in comparison with the contralateral unaffected region; a large, significant effect estimate of 1.85 (95% CI: .95 to 2.75, P < .00001) in favor of worse tactile acuity at the site of pain was noted. This equates to a difference of 1.4 mm (95% CI: .7 mm to 2.0 mm), or a percentage difference of 58% (95% CI: 29% to 86%) between affected and unaffected sides.

      Relationship Between Tactile Acuity and Pain Intensity

      Seven studies
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      reported the relationship between tactile acuity and pain intensity, and the relationship could be calculated from the raw data of 1 further study.
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      Table 3 shows the correlation data for the 8 studies, and Fig 5 compares tactile acuity and current pain intensity for the 6 studies that provided raw tactile acuity and pain intensity data.
      Table 3Relationship Between Tactile Acuity and Pain Intensity
      StudyConditionnPain MeasureRelationship (Pearson's r)Significance (P)
      Lewis and Schweinhardt
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      CRPS22NPSI (average; past 24 h).31>.05
      Maihöfner and DeCol
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      CRPS12NRS−.01>.05
      MPQ-PRI.70<.05
      Moseley
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      CLBP6VAS (current).278
      Spearman's rho.
      Calculated from raw data.
      .298
      VAS (usual)−.213
      Spearman's rho.
      Calculated from raw data.
      .428
      Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      CRPS30MPQ-PRI (current).70<.05
      NRS (posttesting)−.10>.05
      Pleger et al
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      CRPS17NRS (average; past 4 wk).71.001
      NRS (current).36.157
      Reiswich et al
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      CRPS16DASH (average; past 4 wk).39>.05
      NRS (current)−.03>.05
      Stanton et al
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      OA knee20NRS (current)?
      Spearman's rho.
      .170
      NRS (average; past 48 h)?
      Spearman's rho.
      .160
      CLBP17NRS (current)?
      Spearman's rho.
      .870
      NRS (average; past 48 h)?
      Spearman's rho.
      .610
      Wand et al
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      CLBP19NRS (usual).03.914
      NRS (current).015.955
      NRS (worst).032.907
      Abbreviations: VAS, visual analog scale; DASH, Disabilities of the Arm, Shoulder and Hand questionnaire.
      NOTE. Bold highlights significant relationship.?, correlation coefficient calculated but not reported in study.
      Spearman's rho.
      Calculated from raw data.
      Figure thumbnail gr5
      Figure 5Scatterplots showing the relationship between the TPDT and pain intensity (11-point NRS) for people with (A) CRPS; (B) CLBP; (C) chronic knee OA; and (D) combined data (z scores). Note: *, 6-point (0–5) scale Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire (question 24) converted to 11-point NRS; ‡, 0–100 mm visual analog scale converted to 11-point NRS.
      A significant positive relationship between tactile acuity and pain intensity was noted in 3 of 7 studies, all in CRPS samples. Maihöfner and DeCol
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      (n = 12) reported a statistically significant relationship between tactile acuity and current pain intensity (r = .70, P < .05) using the MPQ pain rating index (MPQ-PRI) but not for spontaneous pain intensity measured with a 0 to 100 NRS (r = −.10, P > .05). Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      (n = 30), using the same measures, reported results identical to those of the Maihöfner and DeCol
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      study (see Appendix). Pleger et al
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      (n = 17) noted a statistically significant relationship between tactile acuity and average pain intensity (P = .001) but not current pain intensity (P = .157), both using the NRS. Analysis of the pooled data showed no significant association between tactile acuity and pain intensity (P = .218).

      Relationship Between Tactile Acuity and Pain Duration

      Two studies
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      • Wand B.M.
      • O'Connell N.E.
      Chronic non-specific low back pain—Sub-groups or a single mechanism?.
      reported the relationship between tactile acuity and pain duration. Raw data were available for both of these studies and for a further 3 studies
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      that did not report the relationship. Fig 6 plots the data for people with OA (hands and knee), RA (hands), CRPS, and CLBP.
      Figure thumbnail gr6
      Figure 6Scatterplots showing the relationship between the TPDT and pain duration (months) for people with (A) CRPS; (B) CLBP; (C) chronic knee OA; (D) chronic hand OA; (E) RA; and (F) combined data (z scores).
      Stanton et al
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      noted that pain duration was not related to TPDTs in people with knee OA (n = 20, P = .60) or CLBP (n = 17, P = .61). Wand et al
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      (n = 19) also found no significant correlation between TPDTs and the duration of CLBP (partial r = −.169, P = .516). The raw data from the Ayhan et al
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      (n = 43 OA, 28 RA), Moseley
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      (n = 6), and Pleger et al
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      (n = 17) studies were analyzed, and no further significant relationships were identified between TPDTs and pain duration (P > .90). Analysis of the pooled data showed no significant association between tactile acuity and pain duration (P = .242).

      Discussion

      We aimed to systematically evaluate the literature and use meta-analytical methods to establish whether tactile acuity is altered in people with non-neuropathic chronic pain. The overall pooled results suggest that the tactile acuity of people with non-neuropathic chronic pain is worse at both the site of pain and regions remote from the site of pain in comparison to control individuals. However, the reduction in acuity observed at remote sites is only clearly present in the arthritis data. Although tactile acuity deficits were not evident in all of the included chronic pain conditions, none of the included studies associated chronic pain with an enhancement of tactile acuity.
      In CRPS, there is consistent evidence showing that tactile acuity, assessed at the fingertip, is worse in the affected hand than in both the unaffected hand and the hands of pain-free controls, suggesting that the impairment is restricted to the area of pain. Given the association between tactile acuity and S1 representation,
      • Duncan R.O.
      • Boynton G.M.
      Tactile hyperacuity thresholds correlate with finger maps in primary somatosensory cortex (S1).
      these findings are in keeping with evidence of an altered cortical representation of the affected hand, as compared to the unaffected hand, in people with CRPS
      • Juottonen K.
      • Gockel M.
      • Silén T.
      • Hurri H.
      • Hari R.
      • Forss N.
      Altered central sensorimotor processing in patients with complex regional pain syndrome.
      • Maihöfner C.
      • Handwerker H.O.
      • Neundorfer B.
      • Birklein F.
      Patterns of cortical reorganization in complex regional pain syndrome.
      (see Di Pietro et al
      • Di Pietro F.
      • McAuley J.H.
      • Parkitny L.
      • Lotze M.
      • Wand B.M.
      • Moseley G.L.
      • Stanton T.R.
      Primary somatosensory cortex function in complex regional pain syndrome: A systematic review and meta-analysis.
      for a review).
      We found consistent evidence to suggest that tactile acuity deficits in people with CLBP are restricted to the painful back region. As with the CRPS data, these findings appear to be consistent with cortical reorganization at the back
      • Flor H.
      • Elbert T.
      • Braun C.
      • Birbaumer N.
      Extensive reorganization of primary somatosensory cortex in chronic back pain patients.
      ; however, we are not aware of any data to suggest that S1 representation is normal in unaffected regions.
      In arthritic conditions, we found evidence of altered acuity at both the site of pain and remote regions, suggesting that acuity is generally altered across the body. However, Stanton et al
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      categorized the contralateral knee as unaffected if it was pain free at the time of testing. That many of the participants reported a history of pain in the unaffected knee
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      and that current pain intensity does not correlate with tactile acuity may account for the deficits observed in the remote region. Furthermore, Batterman
      • Batterman R.C.
      Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
      failed to report which joints were affected, and it is possible that joints near the assessment site on the forearm (ie, the wrist) were affected and inflated the size of the difference at the remote site. Although cortical changes are thought to contribute to the pain associated with OA and RA,
      • Lee Y.C.
      • Nassikas N.J.
      • Clauw D.J.
      The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia.
      • Parks E.L.
      • Geha P.Y.
      • Baliki M.N.
      • Katz J.
      • Schnitzer T.J.
      • Apkarian A.V.
      Brain activity for chronic knee osteoarthritis: Dissociating evoked pain from spontaneous pain.
      we are not aware of any evidence of cortical reorganization in these conditions. That deficits in acuity may not be isolated to the region of pain suggests that S1 reorganization alone may not account for the impairment and that other cortical or subcortical areas might be involved. Nonetheless, arthritic conditions are associated with altered touch perception
      • Hendiani J.A.
      • Westlund K.N.
      • Lawand N.
      • Goel N.
      • Lisse J.
      • McNearney T.
      Mechanical sensation and pain thresholds in patients with chronic arthropathies.
      and pain thresholds,
      • Hendiani J.A.
      • Westlund K.N.
      • Lawand N.
      • Goel N.
      • Lisse J.
      • McNearney T.
      Mechanical sensation and pain thresholds in patients with chronic arthropathies.
      • Imamura M.
      • Imamura S.T.
      • Kaziyama H.H.S.
      • Targino R.A.
      • Hsing W.T.
      • De Souza L.P.M.
      • Cutait M.M.
      • Fregni F.
      • Camanho G.L.
      Impact of nervous system hyperalgesia on pain, disability, and quality of life in patients with knee osteoarthritis: A controlled analysis.
      • Martinez V.
      • Fletcher D.
      • Bouhassira D.
      • Sessler D.I.
      • Chauvin M.
      The evolution of primary hyperalgesia in orthopedic surgery: Quantitative sensory testing and clinical evaluation before and after total knee arthroplasty.
      indicative of peripheral and central sensitization,
      • Meeus M.
      • Vervisch S.
      • De Clerck L.S.
      • Moorkens G.
      • Hans G.
      • Nijs J.
      Central sensitization in patients with rheumatoid arthritis: A systematic literature review.
      • Rolke R.
      • Birklein F.
      • Bötefür I.C.
      • Sprenger T.
      • Birbaumer N.
      • Binder A.
      • Tölle T.R.
      • Maier C.
      • Treede R.D.
      • Baron R.
      • Rolko C.
      • Valet M.
      • Huge V.
      • Wasserka B.
      • Scherens A.
      • Klug R.
      • Maihöfner C.
      • Flor H.
      • Beyer A.
      • Schaub C.
      • Braune S.
      • Magerl W.
      • Landwehrmeyer G.B.
      Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values.
      and hyperalgesia, a marker of central sensitization, directly relates to the extent of cortical reorganization in other chronic pain conditions.
      • Maihöfner C.
      • Handwerker H.O.
      • Neundorfer B.
      • Birklein F.
      Patterns of cortical reorganization in complex regional pain syndrome.
      Further studies, using appropriate protocols and remote sites, are needed to further interrogate this phenomenon in arthritic conditions.
      Only 1 study
      • Grushka M.
      • Sessle B.J.
      • Howley T.P.
      Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
      investigated tactile acuity in burning mouth syndrome and found no differences in comparison to healthy controls. This poorly understood condition is thought to be mediated centrally,
      • Gracely R.H.
      • Elias E.
      Psychophysics of pain.
      but to date there is no evidence of cortical reorganization in the burning mouth syndrome literature. That no differences between touch perception or tactile acuity were observed suggests that burning mouth syndrome is not associated with peripheral neural abnormalities or disruption of the sensory neuraxis.
      Tactile acuity does not appear to worsen as pain worsens or persists in the period 3 months after the initial injury. We found little evidence of a relationship between tactile acuity and pain intensity. A significant relationship between tactile acuity and pain intensity was noted only in 3 studies, each in CRPS samples. The identical findings of Maihöfner and DeCol
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      and Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      suggested a significant relationship between acuity and current pain intensity. Conversely, Pleger et al
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      reported a significant relationship between acuity and average pain intensity but found no relationship between acuity and current pain intensity. These conflicting results, and the fact that no further relationships were identified in our analysis of 5 additional data sets, suggest that tactile acuity deficits may be independent of the perceived intensity of the pain. This is surprising given the relationship between tactile acuity and S1 representation
      • Duncan R.O.
      • Boynton G.M.
      Tactile hyperacuity thresholds correlate with finger maps in primary somatosensory cortex (S1).
      and between the extent of S1 reorganization and average pain intensity in both CRPS
      • Maihöfner C.
      • Handwerker H.O.
      • Neundorfer B.
      • Birklein F.
      Patterns of cortical reorganization in complex regional pain syndrome.
      • Maihöfner C.
      • Handwerker H.O.
      • Neundörfer B.
      • Birklein F.
      Cortical reorganization during recovery from complex regional pain syndrome.
      • Pleger B.
      • Tegenthoff M.
      • Schwenkreis P.
      • Janssen F.
      • Ragert P.
      • Dinse H.R.
      • Völker B.
      • Zenz M.
      • Maier C.
      Mean sustained pain levels are linked to hemispherical side-to-side differences of primary somatosensory cortex in the complex regional pain syndrome I.
      and phantom limb pain.
      • Flor H.
      • Elbert T.
      • Knecht S.
      • Wienbruch C.
      • Pantev C.
      • Birbaumer N.
      • Larbig W.
      • Taub E.
      Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.
      • Flor H.
      • Elbert T.
      • Mühlnickel W.
      • Pantev C.
      • Wienbruch C.
      • Taub E.
      Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees.
      • Grüsser S.M.
      • Winter C.
      • Mühlnickel W.
      • Denke C.
      • Karl A.
      • Villringer K.
      • Flor H.
      The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees.
      Although S1 hyperactivity increases with chronicity in CLBP,
      • Flor H.
      • Elbert T.
      • Braun C.
      • Birbaumer N.
      Extensive reorganization of primary somatosensory cortex in chronic back pain patients.
      we found no evidence of a relationship between pain duration and tactile acuity. These findings suggest that tactile acuity does not worsen as pain persists and imply that S1 hyperactivity is not directly related to deficits in tactile acuity. However, the available data regarding these relationships are limited. It is, nonetheless, plausible that the changes in tactile acuity occur in the acute and subacute phases and we were unable to detect a relationship because we only included studies of participants with pain that has persisted for greater than 3 months.
      Although some chronic non-neuropathic pain conditions appear to be associated with deficits in tactile acuity, the point at which a deficit becomes clinically meaningful remains unknown. However, previous studies have addressed the issue of assessment and provided guidelines as to the size of the difference needed to be distinguishable from measurement error.
      • Wand B.M.
      • Catley M.J.
      • Luomajoki H.
      • O'Sullivan K.J.
      • Di Pietro F.
      • O'Connell N.E.
      • Moseley G.L.
      Lumbar tactile acuity is near identical between sides in healthy pain-free participants.
      All of the included studies used the TPDT as a measure of tactile acuity, and the differences between the assessment protocols and tools likely contributed to the observed heterogeneity. The TPDT is the most common measure of tactile acuity
      • Jerosch-Herold C.
      Assessment of sensibility after nerve injury and repair: A systematic review of evidence for validity, reliability and responsiveness of tests.
      as it is easy to assess and is appropriate for use in regions of high and low acuity.
      • Catley M.J.
      • Tabor A.
      • Wand B.M.
      • Moseley G.L.
      Assessing tactile acuity in rheumatology and musculoskeletal medicine: How good are two point discrimination tests at the neck, hand, back and foot?.
      However, it has been criticized for the unexplained variability observed within subjects,
      • Wand B.M.
      • Catley M.J.
      • Luomajoki H.
      • O'Sullivan K.J.
      • Di Pietro F.
      • O'Connell N.E.
      • Moseley G.L.
      Lumbar tactile acuity is near identical between sides in healthy pain-free participants.
      between subjects, and between studies,
      • Johnson K.O.
      • Van Boven R.W.
      • Hsiao S.S.
      The perception of two points is not the spatial resolution threshold.
      and some researchers argue that it should not be used as a scientific measure of acuity.
      • Craig J.C.
      • Johnson K.O.
      The two-point threshold: Not a measure of tactile spatial resolution.
      It is vulnerable to bias insofar as most protocols require the assessor to make a subjective judgment as to when the threshold has been determined. Future studies should consider other measures of tactile acuity such as grating orientation tasks
      • Goldstein E.B.
      Tactile acuity.
      and consider the influence of assessor bias and test-retest reliability. Nonetheless, despite wide variability and small sample sizes, most of the studies included in this review reported statistically significant findings.
      All of the included studies were at risk of bias, primarily because of nonconsecutive recruitment, the lack of exclusion based on recognized diagnosis criteria, and the use of nonblinded assessors. Furthermore, although it is well documented that tactile performance declines with age,
      • Kaneko A.
      • Asai N.
      • Kanda T.
      The influence of age on pressure perception of static and moving two-point discrimination in normal subjects.
      • Woodward K.L.
      The relationship between skin compliance, age, gender, and tactile discrimination thresholds in humans.
      few studies reported age-matching their control group. It is thus plausible that the effect estimates reported in this review may overestimate the true disparity in acuity between people with chronic pain and controls. The fact that all of the included studies that hypothesized that tactile acuity would be altered because of cortical reorganization were statistically significant,
      • Lewis J.S.
      • Schweinhardt P.
      Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
      • Luomajoki H.
      • Moseley G.L.
      Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      • Pleger B.
      • Ragert P.
      • Schwenkreis P.
      • Förster A.F.
      • Wilimzig C.
      • Dinse H.R.
      • Nicolas V.
      • Maier C.
      • Tegenthoff M.
      Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
      • Reiswich J.
      • Krumova E.K.
      • David M.
      • Stude P.
      • Tegenthoff M.
      • Maier C.
      Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      despite the small samples and the wide variability associated with tests of acuity, suggests that a publication bias may also have influenced our results.
      • Lijmer J.G.
      • Mol B.W.
      • Heisterkamp S.
      • Bonsel G.J.
      • Prins M.H.
      • van der Meulen J.H.P.
      • Bossuyt P.M.M.
      Empirical evidence of design-related bias in studies of diagnostic tests.
      Several limitations may have influenced our findings. We only excluded studies that provided explicit evidence of overt peripheral neuropathy. Impaired touch perception can be indicative of nerve injury
      • Maier C.
      • Geber C.
      • Huge V.
      • Birklein F.
      • Flor H.
      • Gierthmühlen J.
      • Birbaumer N.
      • Binder A.
      • Tölle T.R.
      • Baron R.
      Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes.
      and will likely impair tactile acuity, yet only 4 studies
      • Ayhan F.F.
      • Gul S.
      • Uyar S.
      • Erdem H.R.
      • Borman P.
      Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
      • Grushka M.
      • Sessle B.J.
      • Howley T.P.
      Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Wand B.M.
      • Di Pietro F.
      • George P.
      • O'Connell N.E.
      Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
      provided evidence of normal sensory detection. Additionally, none of the CRPS studies included nerve conduction velocity or electromyographic assessments to exclude nerve lesions, which suggests that CRPS (type 2) cannot be ruled out definitively.
      • Borchers A.T.
      • Gershwin M.E.
      Complex regional pain syndrome: A comprehensive and critical review.
      We also did not restrict the age range of the participants, and several of the studies included older adults. Tactile acuity progressively declines across the life span,
      • Bowden J.L.
      • McNulty P.A.
      Age-related changes in cutaneous sensation in the healthy human hand.
      • Kalisch T.
      • Ragert P.
      • Schwenkreis P.
      • Dinse H.R.
      • Tegenthoff M.
      Impaired tactile acuity in old age is accompanied by enlarged hand representations in somatosensory cortex.
      and age-matching was not consistently achieved. It is plausible that some of the observed deficits in acuity were due to peripheral abnormalities or due to age-related changes. Two of the studies used controls that were not pain free,
      • Moseley G.L.
      I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
      • Stanton T.R.
      • Lin C.W.C.
      • Bray H.
      • Smeets R.J.E.M.
      • Taylor D.
      • Law R.
      • Moseley G.L.
      Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
      and 1 study did not include a control group.
      • Saeidian S.R.
      • Moghaddam H.F.
      • Ahangarpour A.
      • Latifi S.M.
      Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
      It is unknown whether these data inflated the differences between the groups or reduced them. Finally, the tactile acuity data reported by Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      differed substantially from the other CRPS studies. The effect sizes from that study were up to 5 times larger than the pooled estimates, and well beyond .8, which is the generally accepted size of a “large” effect.
      • Cohen J.
      Statistical Power Analysis for the Behavioral Sciences.
      The authors assured us that the anomalies in that data (see Appendix) were coincidental, but the possibility of reporting errors cannot be excluded. We undertook sensitivity analyses with the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      data removed to ensure that these outlying results did not carry the main finding. Although the pooled effect sizes and heterogeneity were reduced, the findings remained consistent, with the exception of the finding that tactile acuity was altered at sites remote from the painful site. The sensitivity analysis suggested that TPDTs are not altered at remote sites, and we thus contend that the most prudent position is to conclude that a difference between acuity at sites remote from the site of pain probably does not exist.
      In summary, the current evidence suggests that tactile acuity is altered in several chronic pain conditions. However, the strength of the available evidence is weakened by the inconsistent results and the high risk of bias observed in the included studies. Nonetheless, the current findings suggest that tactile acuity deficits may be characteristic of chronic pain in general. Tactile acuity training may be of benefit to the wider range of chronic pain disorders, and clinical trials of this possibility appear warranted.

      Acknowledgments

      The authors would like to thank Elena Krumova, Hannu Luomajoki, Christian Maihöfner, Burkhard Pleger, Tasha Stanton, and Benedict Wand for kindly providing their raw data and responding rapidly to other inquires.

      Appendix

      The tactile acuity data reported by Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      differed substantially from the other CRPS studies and several anomalies were observed. Although they followed the same protocol described in the group's earlier study, Maihöfner and DeCol,
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      they reported much smaller variability; .18 SD compared with .64 SD (note that the Maihöfner and DeCol data was calculated from raw data). Interestingly, the mean values for both the patients and healthy controls were identical in these 2 studies and the standard deviations reported by Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      were identical to the standard error of the means reported by Maihöfner and DeCol.
      • Maihöfner C.
      • DeCol R.
      Decreased perceptual learning ability in complex regional pain syndrome.
      Intriguingly, the pain intensity data differed, yet the relationship between the TPDT and pain intensity (as measured by the MPQ and NRS) in the 2 studies were identical (see Table 3). We contend that this would seem impossible and we therefore suspect an error in reporting. The raw data for the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      study was unfortunately unavailable, but the authors assured us that the data came from separate cohorts and the several identical values were coincidental. We would contend, however, that these data represent an anomaly and have thus contributed to an overestimation of the acuity deficits in the pooled analyses. As such, we thought it prudent to include the Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      data but also undertake sensitivity analyses (see Suppl Figs 1–3 in the Supplementary Material) to ensure that the outlying results from Peltz et al
      • Peltz E.
      • Seifert F.
      • Lanz S.
      • Muller R.
      • Maihöfner C.
      Impaired hand size estimation in CRPS.
      did not carry the main finding. Although the pooled effect sizes and heterogeneity were reduced, the findings remained consistent, with the exception of the finding that tactile acuity was altered at sites remote from the painful site. The sensitivity analysis suggested that TPDTs are not altered at remote sites, and we thus contend that the most prudent position is to conclude that a difference between acuity at sites remote from the site of pain probably does not exist.

      Supplementary Data

      Figure thumbnail figs1
      Supplementary Figure 1Sensitivity analysis with Peltz et al excluded. Forest plot comparing tactile acuity, assessed at the painful region, of people with chronic pain and healthy pain-free controls. Abbreviations: IV, inverse variance; CI, confidence interval. Note: †, bilateral limb pain (mean TPDT); ‡, unilateral limb pain (affected side TPDT); *, sample size reduced to adjust study weighting; •, calculated from raw data.
      Figure thumbnail figs2
      Supplementary Figure 2Sensitivity analysis with Peltz et al excluded. Forest plot comparing tactile acuity, assessed at a location remote from the painful region, of people with chronic pain and healthy pain-free controls. Abbreviations: IV, inverse variance; CI, confidence interval. Note: †, bilateral limb pain (mean TPDT); ‡, unilateral limb pain (affected side TPDT); *, sample size reduced to adjust study weighting; •, calculated from raw data.
      Figure thumbnail figs3
      Supplementary Figure 3Sensitivity analysis with Peltz et al excluded. Forest plot comparing the tactile acuity of the painful region to the tactile acuity of the contralateral unaffected region, in people with chronic pain. Abbreviations: IV, inverse variance; CI, confidence interval. Note: *, sample size reduced to adjust study weighting; •, calculated from raw data.

      References

        • Altman R.
        • Asch E.
        • Bloch D.
        • Bole G.
        • Borenstein D.
        • Brandt K.
        • Christy W.
        • Cooke T.D.
        • Greenwald R.
        • Hochberg M.
        Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee.
        Arthritis Rheum. 1986; 29: 1039-1049
        • Ayhan F.F.
        • Gul S.
        • Uyar S.
        • Erdem H.R.
        • Borman P.
        Impaired median motor and sensory function of the hands in females with rheumatoid arthritis: Comparisons for osteoarthritis and healthy controls.
        Eur J Pain Suppl. 2011; 5: 226
        • Batterman R.C.
        Analgesic evaluation by two-point spatial discrimination: An objective neurophysiologic approach.
        Curr Ther Res Clin Exp. 1966; 8: 555-560
        • Berryman C.
        • Stanton T.R.
        • Bowering K.J.
        • Tabor A.
        • McFarlane A.
        • Moseley G.L.
        Evidence for working memory deficits in chronic pain: A systematic review and meta-analysis.
        Pain. 2013; 154: 1181-1196
        • Borchers A.T.
        • Gershwin M.E.
        Complex regional pain syndrome: A comprehensive and critical review.
        Autoimmun Rev. 2014; 13: 242-265
        • Bowden J.L.
        • McNulty P.A.
        Age-related changes in cutaneous sensation in the healthy human hand.
        Age. 2013; 35: 1077-1089
        • Bowering K.J.
        • O'Connell N.E.
        • Tabor A.
        • Catley M.J.
        • Leake H.B.
        • Moseley G.L.
        • Stanton T.R.
        The effects of graded motor imagery and its components on chronic pain: A systematic review and meta-analysis.
        J Pain. 2013; 14: 3-13
        • Catley M.J.
        • Tabor A.
        • Wand B.M.
        • Moseley G.L.
        Assessing tactile acuity in rheumatology and musculoskeletal medicine: How good are two point discrimination tests at the neck, hand, back and foot?.
        Rheumatology (Oxford). 2013; 52: 1454-1461
        • Cohen J.
        Statistical Power Analysis for the Behavioral Sciences.
        2nd ed. Lawrence Erlbaum, Hillsdale, NJ1988
        • Craig J.C.
        • Johnson K.O.
        The two-point threshold: Not a measure of tactile spatial resolution.
        Curr Dir Psychol Sci. 2000; 9: 29-32
        • Di Pietro F.
        • McAuley J.H.
        • Parkitny L.
        • Lotze M.
        • Wand B.M.
        • Moseley G.L.
        • Stanton T.R.
        Primary somatosensory cortex function in complex regional pain syndrome: A systematic review and meta-analysis.
        J Pain. 2013; 14: 1001-1018
        • Duncan R.O.
        • Boynton G.M.
        Tactile hyperacuity thresholds correlate with finger maps in primary somatosensory cortex (S1).
        Cereb Cortex. 2007; 17: 2878-2891
        • Flor H.
        • Elbert T.
        • Knecht S.
        • Wienbruch C.
        • Pantev C.
        • Birbaumer N.
        • Larbig W.
        • Taub E.
        Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.
        Nature. 1995; 375: 482-484
        • Flor H.
        • Elbert T.
        • Braun C.
        • Birbaumer N.
        Extensive reorganization of primary somatosensory cortex in chronic back pain patients.
        Neurosci Lett. 1997; 224: 5-8
        • Flor H.
        • Elbert T.
        • Mühlnickel W.
        • Pantev C.
        • Wienbruch C.
        • Taub E.
        Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees.
        Exp Brain Res. 1998; 119
        • Flor H.
        • Denke C.
        • Schaefer M.
        • Grüsser S.
        Effect of sensory discrimination training on cortical reorganisation and phantom limb pain.
        Lancet. 2001; 357: 1763-1764
        • Flor H.
        Cortical reorganisation and chronic pain: Implications for rehabilitation.
        J Rehabil Med. 2003; : 66-72
        • Goldstein E.B.
        Tactile acuity.
        in: Encyclopedia of Perception. Sage Publications, Inc, Thousand Oaks, CA2010: 948-951
        • Gracely R.H.
        • Elias E.
        Psychophysics of pain.
        in: Basbaum A.I. Bushnell C. Science of Pain. Elsevier Academic Press, Philadelphia, PA2009
        • Grushka M.
        • Sessle B.J.
        • Howley T.P.
        Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome.
        Pain. 1987; 28: 169-184
        • Grüsser S.M.
        • Winter C.
        • Mühlnickel W.
        • Denke C.
        • Karl A.
        • Villringer K.
        • Flor H.
        The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees.
        Neuroscience. 2001; 102: 263-272
        • Harden R.N.
        • Bruehl S.P.
        Diagnosis of complex regional pain syndrome: Signs, symptoms, and new empirically derived diagnostic criteria.
        Clin J Pain. 2006; 22: 415-419
        • Hendiani J.A.
        • Westlund K.N.
        • Lawand N.
        • Goel N.
        • Lisse J.
        • McNearney T.
        Mechanical sensation and pain thresholds in patients with chronic arthropathies.
        J Pain. 2003; 4: 203-211
      1. Higgins JPT, Green S (eds): Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available at: http://www.cochrane-handbook.org. Accessed December 2013

        • Imamura M.
        • Imamura S.T.
        • Kaziyama H.H.S.
        • Targino R.A.
        • Hsing W.T.
        • De Souza L.P.M.
        • Cutait M.M.
        • Fregni F.
        • Camanho G.L.
        Impact of nervous system hyperalgesia on pain, disability, and quality of life in patients with knee osteoarthritis: A controlled analysis.
        Arthritis Care Res. 2008; 59: 1424-1431
        • Jerosch-Herold C.
        Assessment of sensibility after nerve injury and repair: A systematic review of evidence for validity, reliability and responsiveness of tests.
        J Hand Surg Am. 2005; 30: 252-264
        • Johnson K.O.
        • Van Boven R.W.
        • Hsiao S.S.
        The perception of two points is not the spatial resolution threshold.
        in: Boivie J. Hansson P. Lindblom U. Touch, Temperature, and Pain in Health and Disease: Mechanisms and Assessments. IASP Press, Seattle, WA1994: 389-404
        • Juottonen K.
        • Gockel M.
        • Silén T.
        • Hurri H.
        • Hari R.
        • Forss N.
        Altered central sensorimotor processing in patients with complex regional pain syndrome.
        Pain. 2002; 98: 315-323
        • Kalisch T.
        • Ragert P.
        • Schwenkreis P.
        • Dinse H.R.
        • Tegenthoff M.
        Impaired tactile acuity in old age is accompanied by enlarged hand representations in somatosensory cortex.
        Cereb Cortex. 2009; 19: 1530-1538
        • Kaneko A.
        • Asai N.
        • Kanda T.
        The influence of age on pressure perception of static and moving two-point discrimination in normal subjects.
        J Hand Ther. 2005; 18: 421-425
        • Lee Y.C.
        • Nassikas N.J.
        • Clauw D.J.
        The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia.
        Arthritis Res Ther. 2011; 13: 211
        • Lewis J.S.
        • Schweinhardt P.
        Perceptions of the painful body: The relationship between body perception disturbance, pain and tactile discrimination in complex regional pain syndrome.
        Eur J Pain. 2012; 16: 1320-1330
        • Lijmer J.G.
        • Mol B.W.
        • Heisterkamp S.
        • Bonsel G.J.
        • Prins M.H.
        • van der Meulen J.H.P.
        • Bossuyt P.M.M.
        Empirical evidence of design-related bias in studies of diagnostic tests.
        J Am Med Assoc. 1999; 282: 1061-1066
        • Luomajoki H.
        • Moseley G.L.
        Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls.
        Br J Sports Med. 2011; 45: 437-440
        • Maier C.
        • Geber C.
        • Huge V.
        • Birklein F.
        • Flor H.
        • Gierthmühlen J.
        • Birbaumer N.
        • Binder A.
        • Tölle T.R.
        • Baron R.
        Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes.
        Pain. 2010; 150: 439-450
        • Maihöfner C.
        • Handwerker H.O.
        • Neundorfer B.
        • Birklein F.
        Patterns of cortical reorganization in complex regional pain syndrome.
        Neurology. 2003; 61: 1707-1715
        • Maihöfner C.
        • DeCol R.
        Decreased perceptual learning ability in complex regional pain syndrome.
        Eur J Pain. 2007; 11: 903-909
        • Maihöfner C.
        • Handwerker H.O.
        • Neundörfer B.
        • Birklein F.
        Cortical reorganization during recovery from complex regional pain syndrome.
        Neurology. 2004; 63: 693-701
        • Maihöfner C.
        • Neundörfer B.
        • Birklein F.
        • Handwerker H.O.
        Mislocalization of tactile stimulation in patients with complex regional pain syndrome.
        J Neurol. 2006; 253: 772-779
        • Martinez V.
        • Fletcher D.
        • Bouhassira D.
        • Sessler D.I.
        • Chauvin M.
        The evolution of primary hyperalgesia in orthopedic surgery: Quantitative sensory testing and clinical evaluation before and after total knee arthroplasty.
        Anesth Analg. 2007; 105: 815-821
        • Meeus M.
        • Vervisch S.
        • De Clerck L.S.
        • Moorkens G.
        • Hans G.
        • Nijs J.
        Central sensitization in patients with rheumatoid arthritis: A systematic literature review.
        Semin Arthritis Rheum. 2012; 41: 556-567
      2. Merksey H. Bogduk N. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 2nd ed. IASP Press, Seattle, WA1994
        • Merskey H.
        • Bogduk N.
        Classification of Chronic Pain, IASP Task Force on Taxonomy.
        IASP Press, Seattle, WA1994
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement.
        PLoS Med. 2009; 6: e1000097
        • Moseley G.L.
        I can't find it! Distorted body image and tactile dysfunction in patients with chronic back pain.
        Pain. 2008; 140: 239-243
        • Moseley G.L.
        • Zalucki N.M.
        • Wiech K.
        Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain.
        Pain. 2008; 137: 600-608
        • Moseley G.L.
        • Wiech K.
        The effect of tactile discrimination training is enhanced when patients watch the reflected image of their unaffected limb during training.
        Pain. 2009; 144: 314-319
        • Moseley G.L.
        • Flor H.
        Targeting cortical representations in the treatment of chronic pain: A review.
        Neurorehabil Neural Repair. 2012; 26: 646-652
        • Parks E.L.
        • Geha P.Y.
        • Baliki M.N.
        • Katz J.
        • Schnitzer T.J.
        • Apkarian A.V.
        Brain activity for chronic knee osteoarthritis: Dissociating evoked pain from spontaneous pain.
        Eur J Pain. 2011; 15: 843.e1-843.e14
        • Peltz E.
        • Seifert F.
        • Lanz S.
        • Muller R.
        • Maihöfner C.
        Impaired hand size estimation in CRPS.
        J Pain. 2011; 12: 1095-1101
        • Peters M.L.
        • Schmidt A.J.M.
        A comparison of two-point discrimination threshold of tactual, non-painful stimuli between chronic low back pain patients and controls.
        Pain. 1991; 44: 57-60
        • Pleger B.
        • Dinse H.R.
        • Ragert P.
        • Schwenkreis P.
        • Malin J.P.
        • Tegenthoff M.
        Shifts in cortical representations predict human discrimination improvement.
        Proc Natl Acad Sci U S A. 2001; 98: 12255-12260
        • Pleger B.
        • Tegenthoff M.
        • Schwenkreis P.
        • Janssen F.
        • Ragert P.
        • Dinse H.R.
        • Völker B.
        • Zenz M.
        • Maier C.
        Mean sustained pain levels are linked to hemispherical side-to-side differences of primary somatosensory cortex in the complex regional pain syndrome I.
        Exp Brain Res. 2004; 155: 115-119
        • Pleger B.
        • Ragert P.
        • Schwenkreis P.
        • Förster A.F.
        • Wilimzig C.
        • Dinse H.R.
        • Nicolas V.
        • Maier C.
        • Tegenthoff M.
        Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
        Neuroimage. 2006; 32: 503-510
        • Reiswich J.
        • Krumova E.K.
        • David M.
        • Stude P.
        • Tegenthoff M.
        • Maier C.
        Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.
        Pain. 2012; 153: 1484-1494
        • Rolke R.
        • Birklein F.
        • Bötefür I.C.
        • Sprenger T.
        • Birbaumer N.
        • Binder A.
        • Tölle T.R.
        • Maier C.
        • Treede R.D.
        • Baron R.
        • Rolko C.
        • Valet M.
        • Huge V.
        • Wasserka B.
        • Scherens A.
        • Klug R.
        • Maihöfner C.
        • Flor H.
        • Beyer A.
        • Schaub C.
        • Braune S.
        • Magerl W.
        • Landwehrmeyer G.B.
        Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values.
        Pain. 2006; 123: 231-243
        • Rossini P.
        • Martino G.
        • Narici L.
        • Pasquarelli A.
        • Peresson M.
        • Pizzella V.
        • Tecchio F.
        • Torrioli G.
        • Romani G.
        Short-term brain “plasticity” in humans: Transient finger representation changes in sensory cortex somatotopy following ischemic anesthesia.
        Brain Res. 1994; 642: 169-177
        • Saeidian S.R.
        • Moghaddam H.F.
        • Ahangarpour A.
        • Latifi S.M.
        Two-point discrimination test in the treatment of right-handed females with lumbosacral radiculopathy.
        Iran J Med Sci. 2011; 36: 296-299
        • Seltzer S.F.
        • Seltzer J.L.
        Tactual sensitivity of chronic pain patients to non-painful stimuli.
        Pain. 1986; 27: 291-295
        • Seltzer S.F.
        • Yarczower M.
        • Woo R.
        • Seltzer J.L.
        Laterality and modality-specific effects of chronic pain.
        Percept Psychophys. 1992; 51: 500-503
        • Stanton T.R.
        • Lin C.W.C.
        • Bray H.
        • Smeets R.J.E.M.
        • Taylor D.
        • Law R.
        • Moseley G.L.
        Tactile acuity is disrupted in osteoarthritis but is unrelated to disruptions in motor imagery performance.
        Rheumatology (Oxford). 2013; 52: 1509-1519
        • Tecchio F.
        • Padua L.
        • Aprile I.
        • Rossini P.M.
        Carpal tunnel syndrome modifies sensory hand cortical somatotopy: A MEG study.
        Hum Brain Mapp. 2002; 17: 28-36
        • van Rijn M.A.
        • van Hilten J.J.
        • van Dijk J.G.
        Spatiotemporal integration of sensory stimuli in complex regional pain syndrome and dystonia.
        J Neural Transm. 2009; 116: 559-565
        • Vartiainen N.V.
        • Kirveskari E.
        • Forss N.
        Central processing of tactile and nociceptive stimuli in complex regional pain syndrome.
        Clin Neurophysiol. 2008; 119: 2380-2388
        • Vartiainen N.V.
        • Kirveskari E.
        • Kallio-Laine K.
        • Kalso E.
        • Forss N.
        Cortical reorganization in primary somatosensory cortex in patients with unilateral chronic pain.
        J Pain. 2009; 10: 854-859
        • von Elm E.
        • Altman D.G.
        • Egger M.
        • Pocock S.J.
        • Gotzsche P.C.
        • Vanderbroucke J.P.
        The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies.
        PLoS Med. 2007; 4: e296
        • Wand B.M.
        • O'Connell N.E.
        Chronic non-specific low back pain—Sub-groups or a single mechanism?.
        BMC Musculoskelet Disord. 2008; 9: 11
        • Wand B.M.
        • Di Pietro F.
        • George P.
        • O'Connell N.E.
        Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: A preliminary investigation.
        Physiotherapy. 2010; 96: 317-323
        • Wand B.M.
        • O'Connell N.E.
        • Di Pietro F.
        • Bulsara M.
        Managing chronic nonspecific low back pain with a sensorimotor retraining approach: Exploratory multi-baseline study of 3 participants.
        Phys Ther. 2011; 91: 535-546
        • Wand B.M.
        • Abbaszadeh S.
        • Smith A.J.
        • Catley M.J.
        • Moseley G.L.
        Acupuncture applied as a sensory discrimination training tool decreases movement related pain in chronic low back pain patients more than acupuncture alone: A randomised cross-over experiment.
        Br J Sports Med. 2013; 47: 1085-1089
        • Wand B.M.
        • Catley M.J.
        • Luomajoki H.
        • O'Sullivan K.J.
        • Di Pietro F.
        • O'Connell N.E.
        • Moseley G.L.
        Lumbar tactile acuity is near identical between sides in healthy pain-free participants.
        Man Ther. 2014 Jan 18; ([Epub ahead of print])
        • Woodward K.L.
        The relationship between skin compliance, age, gender, and tactile discrimination thresholds in humans.
        Somatosens Mot Res. 1993; 10: 63-67