Advertisement

Individual Variation in Pain Sensitivity and Conditioned Pain Modulation in Acute Low Back Pain: Effect of Stimulus Type, Sleep, and Psychological and Lifestyle Factors

  • David M. Klyne
    Affiliations
    The University of Queensland, NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, Brisbane, Australia
    Search for articles by this author
  • G. Lorimer Moseley
    Affiliations
    The University of South Australia, The Sansom Institute for Health Research, Adelaide, Australia

    Neuroscience Research Australia, Sydney, Australia
    Search for articles by this author
  • Michele Sterling
    Affiliations
    Recover Injury Research Centre, NHMRC CRE in Recovery after Road Traffic Injury, Griffith University, Southport, Australia
    Search for articles by this author
  • Mary F. Barbe
    Affiliations
    Temple University, Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania
    Search for articles by this author
  • Paul W. Hodges
    Correspondence
    Address reprint requests to Paul W. Hodges, PhD, MedDr, DSc, BPhty(Hons) FACP, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
    Affiliations
    The University of Queensland, NHMRC Centre of Clinical Research Excellence in Spinal Pain, Injury and Health, School of Health and Rehabilitation Sciences, Brisbane, Australia
    Search for articles by this author

      Highlights

      • Enhanced sensitivity consistent with generalized hyperalgesia was observed.
      • Acute back pain includes 4 subgroups with sensitivity and modulation profiles.
      • Various factors including sleep and alcohol explain some variation in presentation.

      Abstract

      Generalized hyperalgesia and impaired pain modulation are reported in chronic low back pain (LBP). Few studies have tested whether these features are present in the acute phase. This study aimed to test for differences in pain presentation in early-acute LBP and evaluate the potential contribution of other factors to variation in sensitivity. Individuals within 2 weeks of onset of acute LBP (n = 126) and pain-free controls (n = 74) completed questionnaires related to their pain, disability, behavior, and psychological status before undergoing conditioned pain modulation (CPM) and pain threshold (heat, cold, and pressure) testing at the back and forearm/thumb. LBP participants were more sensitive to heat and cold at both sites and pressure at the back than controls, without differences in CPM. Only those with high-pain (numeric rating scale ≥4) were more sensitive to heat at the forearm and pressure at the back. Four subgroups with distinct features were identified: “high sensitivity,” “low CPM efficacy,” “high sensitivity/low CPM efficacy,” and “low sensitivity/high CPM efficacy.” Various factors such as sleep and alcohol were associated with each pain measure. Results provide evidence for generalized hyperalgesia in many, but not all, individuals during acute LBP, with variation accounted for by several factors. Specific pain phenotypes provide candidate features to test in longitudinal studies of LBP outcome.

      Perspective

      Sensory changes indicative of increased/decreased central processing of pain and nociceptive input presented differently between individuals with acute LBP and were related to factors such as sleep and alcohol. This may underlie variation in outcome and suggest potential for early identification of individuals with poor long-term outcome.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ab Aziz C.B.
        • Ahmad A.H.
        The role of the thalamus in modulating pain.
        Malays J Med Sci. 2006; 13: 11-18
        • Arendt-Nielsen L.
        • Nie H.
        • Laursen M.B.
        • Laursen B.S.
        • Madeleine P.
        • Simonsen O.H.
        • Graven-Nielsen T.
        Sensitization in patients with painful knee osteoarthritis.
        Pain. 2010; 149: 573-581
        • Austin P.C.
        • Steyerberg E.W.
        The number of subjects per variable required in linear regression analyses.
        J Clin Epidemiol. 2015; 68: 627-636
        • Backhaus J.
        • Junghanns K.
        • Broocks A.
        • Riemann D.
        • Hohagen F.
        Test-retest reliability and validity of the Pittsburgh sleep quality index in primary insomnia.
        J Psychosom Res. 2002; 53: 737-740
        • Balague F.
        • Mannion A.F.
        • Pellise F.
        • Cedraschi C.
        Clinical update: Low back pain.
        Lancet. 2007; 369: 726-728
        • Baranauskas G.
        • Nistri A.
        Sensitization of pain pathways in the spinal cord: Cellular mechanisms.
        Prog Neurobiol. 1998; 54: 349-365
        • Blumenstiel K.
        • Gerhardt A.
        • Rolke R.
        • Bieber C.
        • Tesarz J.
        • Friederich H.C.
        • Eich W.
        • Treede R.D.
        Quantitative sensory testing profiles in chronic back pain are distinct from those in fibromyalgia.
        Clin J Pain. 2011; 27: 682-690
        • Boardman H.F.
        • Thomas E.
        • Millson D.S.
        • Croft P.R.
        The natural history of headache: Predictors of onset and recovery.
        Cephalalgia. 2006; 26: 1080-1088
        • Boersma K.
        • Linton S.J.
        How does persistent pain develop? An analysis of the relationship between psychological variables, pain and function across stages of chronicity.
        Behav Res Ther. 2005; 43: 1495-1507
        • Boonstra A.M.
        • Schiphorst Preuper H.R.
        • Balk G.A.
        • Stewart R.E.
        Cut-off points for mild, moderate, and severe pain on the visual analogue scale for pain in patients with chronic musculoskeletal pain.
        Pain. 2014; 155: 2545-2550
        • Bushnell M.C.
        • Duncan G.H.
        • Tremblay N.
        Thalamic VPM nucleus in the behaving monkey. I. Multimodal and discriminative properties of thermosensitive neurons.
        J Neurophysiol. 1993; 69: 739-752
        • Buysse D.J.
        • Reynolds C.F.
        • Monk T.H.
        • Berman S.R.
        • Kupfer D.J.
        The Pittsburgh Sleep Quality Index—a new instrument for psychiatric practice and research.
        Psychiat Res. 1989; 28: 193-213
        • Campbell C.M.
        • Edwards R.R.
        Mind-body interactions in pain: The neurophysiology of anxious and catastrophic pain-related thoughts.
        Transl Res. 2009; 153: 97-101
        • Carpenter J.S.
        • Andrykowski M.A.
        Psychometric evaluation of the Pittsburgh Sleep Quality Index.
        J Psychosom Res. 1998; 45: 5-13
        • Casey K.L.
        • Minoshima S.
        • Morrow T.J.
        • Koeppe R.A.
        Comparison of human cerebral activation patterns during cutaneous warmth, heat pain, and deep cold pain.
        J Neurophysiol. 1996; 76: 571-581
        • Clauw D.J.
        • Williams D.
        • Lauerman W.
        • Dahlman M.
        • Aslami A.
        • Nachemson A.L.
        • Kobrine A.I.
        • Wiesel S.W.
        Pain sensitivity as a correlate of clinical status in individuals with chronic low back pain.
        Spine. 1999; 24: 2035-2041
        • Correa J.B.
        • Costa L.O.
        • de Oliveira N.T.
        • Sluka K.A.
        • Liebano R.E.
        Central sensitization and changes in conditioned pain modulation in people with chronic nonspecific low back pain: A case-control study.
        Exp Brain Res. 2015; 233: 2391-2399
        • Costello A.B.
        • Osborne J.W.
        Best practices in exploratory factor analysis: Four recommendations for getting the most from your analysis.
        Prac Assess Res Eval. 2005; 10
        • Craig A.D.
        • Bushnell M.C.
        • Zhang E.T.
        • Blomqvist A.
        A thalamic nucleus specific for pain and temperature sensation.
        Nature. 1994; 372: 770-773
        • Derbyshire S.W.
        • Jones A.K.
        • Creed F.
        • Starz T.
        • Meltzer C.C.
        • Townsend D.W.
        • Peterson A.M.
        • Firestone L.
        Cerebral responses to noxious thermal stimulation in chronic low back: Pain patients and normal controls.
        Neuroimage. 2002; 16: 158-168
        • Dubin A.E.
        • Patapoutian A.
        Nociceptors: The sensors of the pain pathway.
        J Clin Invest. 2010; 120: 3760-3772
        • Edwards R.R.
        • Almeida D.M.
        • Klick B.
        • Haythornthwaite J.A.
        • Smith M.T.
        Duration of sleep contributes to next-day pain report in the general population.
        Pain. 2008; 137: 202-207
        • Edwards R.R.
        • Wasan A.D.
        • Michna E.
        • Greenbaum S.
        • Ross E.
        • Jamison R.N.
        Elevated pain sensitivity in chronic pain patients at risk for opioid misuse.
        J Pain. 2011; 12: 953-963
        • Fillingim R.B.
        • King C.D.
        • Ribeiro-Dasilva M.C.
        • Rahim-Williams B.
        • Riley 3rd., J.L.
        Sex, gender, and pain: A review of recent clinical and experimental findings.
        J Pain. 2009; 10: 447-485
        • Flor H.
        • Braun C.
        • Elbert T.
        • Birbaumer N.
        Extensive reorganization of primary somatosensory cortex in chronic back pain patients.
        Neurosci Lett. 1997; 224: 5-8
        • Gatchel R.J.
        • Peng Y.B.
        • Peters M.L.
        • Fuchs P.N.
        • Turk D.C.
        The biopsychosocial approach to chronic pain: Scientific advances and future directions.
        Psychol Bull. 2007; 133: 581-624
        • George S.Z.
        • Wittmer V.T.
        • Fillingim R.B.
        • Robinson M.E.
        Fear-avoidance beliefs and temporal summation of evoked thermal pain influence self-report of disability in patients with chronic low back pain.
        J Occup Rehabil. 2006; 16: 95-108
        • George S.Z.
        • Wittmer V.T.
        • Fillingim R.B.
        • Robinson M.E.
        Sex and pain-related psychological variables are associated with thermal pain sensitivity for patients with chronic low back pain.
        J Pain. 2007; 8: 2-10
        • Gibson S.J.
        • Farrell M.
        A review of age differences in the neurophysiology of nociception and the perceptual experience of pain.
        Clin J Pain. 2004; 20: 227-239
        • Giesecke T.
        • Gracely R.H.
        • Grant M.A.
        • Nachemson A.
        • Petzke F.
        • Williams D.A.
        • Clauw D.J.
        Evidence of augmented central pain processing in idiopathic chronic low back pain.
        Arthritis Rheum. 2004; 50: 613-623
        • Goffaux P.
        • Redmond W.J.
        • Rainville P.
        • Marchand S.
        Descending analgesia—when the spine echoes what the brain expects.
        Pain. 2007; 130: 137-143
        • Gold M.S.
        • Gebhart G.F.
        Nociceptor sensitization in pain pathogenesis.
        Nat Med. 2010; 16: 1248-1257
        • Graven-Nielsen T.
        • Mense S.
        • Arendt-Nielsen L.
        Painful and non-painful pressure sensations from human skeletal muscle.
        Exp Brain Res. 2004; 159: 273-283
        • Haack M.
        • Scott-Sutherland J.
        • Santangelo G.
        • Simpson N.S.
        • Sethna N.
        • Mullington J.M.
        Pain sensitivity and modulation in primary insomnia.
        Eur J Pain. 2012; 16: 522-533
        • Hair J.F.
        • Black W.C.
        • Babin B.J.
        Multivariate Data Analysis: A Global Perspective.
        7th ed. Pearson Education, London2010
        • Hamilton N.A.
        • Pressman M.
        • Lillis T.
        • Atchley R.
        • Karlson C.
        • Stevens N.
        Evaluating evidence for the role of sleep in fibromyalgia: A test of the sleep and pain diathesis model.
        Cognit Ther Res. 2012; 36: 806-814
        • Henschke N.
        • Maher C.G.
        • Refshauge K.M.
        • Herbert R.D.
        • Cumming R.G.
        • Bleasel J.
        • York J.
        • Das A.
        • McAuley J.H.
        Prognosis in patients with recent onset low back pain in Australian primary care: Inception cohort study.
        Brit Med J. 2008; 337
        • Hubscher M.
        • Moloney N.
        • Rebbeck T.
        • Traeger A.
        • Refshauge K.M.
        Contributions of mood, pain catastrophizing, and cold hyperalgesia in acute and chronic low back pain: A comparison with pain-free controls.
        Clin J Pain. 2014; 30: 886-893
        • Irwin M.R.
        • Olmstead R.
        • Carrillo C.
        • Sadeghi N.
        • FitzGerald J.D.
        • Ranganath V.K.
        • Nicassio P.M.
        Sleep loss exacerbates fatigue, depression, and pain in rheumatoid arthritis.
        Sleep. 2012; 35: 537-543
        • Jolliffe I.T.
        Choosing a subset of principal components or variables.
        in: Principal Component Analysis. Springer-Verlag, New York2002
        • Julien N.
        • Goffaux P.
        • Arsenault P.
        • Marchand S.
        Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition.
        Pain. 2005; 114: 295-302
        • Kelly G.A.
        • Blake C.
        • Power C.K.
        • O'Keeffe D.
        • Fullen B.M.
        The association between chronic low back pain and sleep a systematic review.
        Clin J Pain. 2011; 27: 169-181
        • Kidd B.L.
        • Urban L.A.
        Mechanisms of inflammatory pain.
        Br J Anaesth. 2001; 87: 3-11
        • Kilo S.
        • Schmelz M.
        • Koltzenburg M.
        • Handwerker H.O.
        Different patterns of hyperalgesia induced by experimental inflammation in human skin.
        Brain. 1994; 117: 385-396
        • Kim J.H.
        • Park E.C.
        • Yoo K.B.
        • Park S.
        The association between short or long sleep times and quality of life (QOL): Results of the Korea National Health and Nutrition Examination Survey (KNHANES IV-V).
        J Clin Sleep Med. 2015; 11: 625-634
        • King C.D.
        • Sibille K.T.
        • Goodin B.R.
        • Cruz-Almeida Y.
        • Glover T.L.
        • Bartley E.
        • Riley J.L.
        • Herbert M.S.
        • Sotolongo A.
        • Schmidt J.
        • Fessler B.J.
        • Redden D.T.
        • Staud R.
        • Bradley L.A.
        • Fillingim R.B.
        Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis.
        Osteoarthritis Cartilage. 2013; 21: 1243-1252
        • Klyne D.M.
        • Schmid A.B.
        • Moseley G.L.
        • Sterling M.
        • Hodges P.W.
        Effect of types and anatomic arrangement of painful stimuli on conditioned pain modulation.
        J Pain. 2015; 16: 176-185
        • Kosek E.
        • Ekholm J.
        • Hansson P.
        Pressure pain thresholds in different tissues in one body region. The influence of skin sensitivity in pressure algometry.
        Scand J Rehabil Med. 1999; 31: 89-93
        • Kundermann B.
        • Spernal J.
        • Huber M.T.
        • Krieg J.C.
        • Lautenbacher S.
        Sleep deprivation affects thermal pain thresholds but not somatosensory thresholds in healthy volunteers.
        Psychosom Med. 2004; 66: 932-937
        • Lariviere M.
        • Goffaux P.
        • Marchand S.
        • Julien N.
        Changes in pain perception and descending inhibitory controls start at middle age in healthy adults.
        Clin J Pain. 2007; 23: 506-510
        • Latremoliere A.
        • Woolf C.J.
        Central sensitization: A generator of pain hypersensitivity by central neural plasticity.
        J Pain. 2009; 10: 895-926
        • Lautenbacher S.
        • Kunz M.
        • Strate P.
        • Nielsen J.
        • Arendt-Nielsen L.
        Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain.
        Pain. 2005; 115: 410-418
        • Lawton J.
        • Simpson J.
        Predictors of alcohol use among people experiencing chronic pain.
        Psychol Health Med. 2009; 14: 487-501
        • Leboeuf-Yde C.
        Alcohol and low-back pain: A systematic literature review.
        J Manipulative Physiol Ther. 2000; 23: 343-346
        • Lenz F.A.
        • Gracely R.H.
        • Rowland L.H.
        • Dougherty P.M.
        A population of cells in the human thalamic principal sensory nucleus respond to painful mechanical stimuli.
        Neurosci Lett. 1994; 180: 46-50
        • Lenz F.A.
        • Seike M.
        • Lin Y.C.
        • Baker F.H.
        • Rowland L.H.
        • Gracely R.H.
        • Richardson R.T.
        Neurons in the area of human thalamic nucleus ventralis caudalis respond to painful heat stimuli.
        Brain Res. 1993; 623: 235-240
        • LeResche L.
        • Turner J.A.
        • Saunders K.
        • Shortreed S.M.
        • Von Korff M.
        Psychophysical tests as predictors of back pain chronicity in primary care.
        J Pain. 2013; 14: 1663-1670
        • Lewinsohn P.M.
        • Seeley J.R.
        • Roberts R.E.
        • Allen N.B.
        Center for Epidemiologic Studies Depression Scale (CES-D) as a screening instrument for depression among community-residing older adults.
        Psychol Aging. 1997; 12: 277-287
        • Lewis G.N.
        • Rice D.A.
        • McNair P.J.
        Conditioned pain modulation in populations with chronic pain: A systematic review and meta-analysis.
        J Pain. 2012; 13: 936-944
        • Linley J.E.
        • Rose K.
        • Ooi L.
        • Gamper N.
        Understanding inflammatory pain: Ion channels contributing to acute and chronic nociception.
        Pflugers Arch. 2010; 459: 657-669
        • Linton S.J.
        A review of psychological risk factors in back and neck pain.
        Spine. 2000; 25: 1148-1156
        • Magee C.A.
        • Caputi P.
        • Iverson D.C.
        Relationships between self-rated health, quality of life and sleep duration in middle aged and elderly Australians.
        Sleep Med. 2011; 12: 346-350
        • Mallen C.D.
        • Peat G.
        • Thomas E.
        • Dunn K.M.
        • Croft P.R.
        Prognostic factors for musculoskeletal pain in primary care: A systematic review.
        Brit J Gen Pract. 2007; 57: 655-661
        • Melzack R.
        Folk Medicine and the Sensory Modulation of Pain.
        3rd ed. Churchill Livingstone, Edinburgh1994
        • Meyer R.A.
        • Ringkamp M.
        • Campbell J.N.
        • Raja S.N.
        Neural mechanisms of hyperalgesia after tissue injury.
        Johns Hopkins APL Tech Dig. 2005; 26: 56-66
        • Millan M.J.
        Descending control of pain.
        Prog Neurobiol. 2002; 66: 355-474
        • Miro E.
        • Martinez M.P.
        • Sanchez A.I.
        • Prados G.
        • Medina A.
        When is pain related to emotional distress and daily functioning in fibromyalgia syndrome? The mediating roles of self-efficacy and sleep quality.
        Brit J Health Psych. 2011; 16: 799-814
        • Mlekusch S.
        • Neziri A.Y.
        • Limacher A.
        • Juni P.
        • Arendt-Nielsen L.
        • Curatolo M.
        Conditioned pain modulation in patients with acute and chronic low back pain.
        Clin J Pain. 2016; 32: 116-121
        • Nahman-Averbuch H.
        • Nir R.R.
        • Sprecher E.
        • Yarnitsky D.
        Psychological factors and conditioned pain modulation: A meta-analysis.
        Clin J Pain. 2016; 32: 541-554
        • Nicholas M.K.
        The pain self-efficacy questionnaire: Taking pain into account.
        Eur J Pain. 2007; 11: 153-163
        • Nijs J.
        • Torres-Cueco R.
        • van Wilgen C.P.
        • Girbes E.L.
        • Struyf F.
        • Roussel N.
        • van Oosterwijck J.
        • Daenen L.
        • Kuppens K.
        • Vanwerweeen L.
        • Hermans L.
        • Beckwee D.
        • Voogt L.
        • Clark J.
        • Moloney N.
        • Meeus M.
        Applying modern pain neuroscience in clinical practice: Criteria for the classification of central sensitization pain.
        Pain Physician. 2014; 17: 447-457
        • Nir R.R.
        • Yarnitsky D.
        • Honigman L.
        • Granot M.
        Cognitive manipulation targeted at decreasing the conditioning pain perception reduces the efficacy of conditioned pain modulation.
        Pain. 2012; 153: 170-176
        • O'Brien E.M.
        • Waxenberg L.B.
        • Atchison J.W.
        • Gremillion H.A.
        • Staud R.M.
        • McCrae C.S.
        • Robinson M.E.
        Negative mood mediates the effect of poor sleep on pain among chronic pain patients.
        Clin J Pain. 2010; 26: 310-319
        • Odegard S.S.
        • Sand T.
        • Engstrom M.
        • Stovner L.J.
        • Zwart J.A.
        • Hagen K.
        The long-term effect of insomnia on primary headaches: A prospective population-based cohort study (HUNT-2 and HUNT-3).
        Headache. 2011; 51: 570-580
        • Onen S.H.
        • Alloui A.
        • Gross A.
        • Eschaller A.
        • Dubray C.
        The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects.
        J Sleep Res. 2001; 10: 35-42
        • O'Neill S.
        • Kjaer P.
        • Graven-Nielsen T.
        • Manniche C.
        • Arendt-Nielsen L.
        Low pressure pain thresholds are associated with, but does not predispose for, low back pain.
        Eur Spine J. 2011; 20: 2120-2125
        • O'Neill S.
        • Manniche C.
        • Graven-Nielsen T.
        • Arendt-Nielsen L.
        Generalized deep-tissue hyperalgesia in patients with chronic low-back pain.
        Eur J Pain. 2007; 11: 415-420
        • Osman A.
        • Barrios F.X.
        • Kopper B.A.
        • Hauptmann W.
        • Jones J.
        • O'Neill E.
        Factor structure, reliability, and validity of the Pain Catastrophizing Scale.
        J Behav Med. 1997; 20: 589-605
        • Ossipov M.H.
        The perception and endogenous modulation of pain.
        Scientifica (Cairo). 2012; 2012: 561761
        • O'Sullivan P.
        • Waller R.
        • Wright A.
        • Gardner J.
        • Johnston R.
        • Payne C.
        • Shannon A.
        • Ware B.
        • Smith A.
        Sensory characteristics of chronic non-specific low back pain: A subgroup investigation.
        Man Ther. 2014; 19: 311-318
        • Pielsticker A.
        • Haag G.
        • Zaudig M.
        • Lautenbacher S.
        Impairment of pain inhibition in chronic tension-type headache.
        Pain. 2005; 118: 215-223
        • Pincus T.
        • Burton A.K.
        • Vogel S.
        • Field A.P.
        A systematic review of psychological factors as predictors of chronicity/disability in prospective cohorts of low back pain.
        Spine. 2002; 27: E109-E120
        • Popescu A.
        • LeResche L.
        • Truelove E.L.
        • Drangsholt M.T.
        Gender differences in pain modulation by diffuse noxious inhibitory controls: A systematic review.
        Pain. 2010; 150: 309-318
        • Pud D.
        • Granovsky Y.
        • Yarnitsky D.
        The methodology of experimentally induced diffuse noxious inhibitory control (DNIC)-like effect in humans.
        Pain. 2009; 144: 16-19
        • Puta C.
        • Schulz B.
        • Schoeler S.
        • Magerl W.
        • Gabriel B.
        • Gabriel H.H.
        • Miltner W.H.
        • Weiss T.
        Somatosensory abnormalities for painful and innocuous stimuli at the back and at a site distinct from the region of pain in chronic back pain patients.
        PLoS One. 2013; 8: e58885
        • Rabey M.
        • Poon C.
        • Wray J.
        • Thamajaree C.
        • East R.
        • Slater H.
        Pro-nociceptive and anti-nociceptive effects of a conditioned pain modulation protocol in participants with chronic low back pain and healthy control subjects.
        Man Ther. 2015; 20: 763-768
        • Radloff L.S.
        The CES-D Scale: A new self-report depression scale for research in the general population.
        Appl Psychol Meas. 1977; 1: 385-401
        • Rezaii T.
        • Hirschberg A.L.
        • Carlstrom K.
        • Ernberg M.
        The influence of menstrual phases on pain modulation in healthy women.
        J Pain. 2012; 13: 646-655
        • Riley 3rd, J.L.
        • King C.D.
        • Wong F.
        • Fillingim R.B.
        • Mauderli A.P.
        Lack of endogenous modulation and reduced decay of prolonged heat pain in older adults.
        Pain. 2010; 150: 153-160
        • Riley J.L.
        • Robinson M.E.
        • Wise E.A.
        • Myers C.D.
        • Fillingim R.B.
        Sex differences in the perception of noxious experimental stimuli: A meta-analysis.
        Pain. 1998; 74: 181-187
        • Roland M.
        • Morris R.
        A study of the natural history of back pain. Part I: Development of a reliable and sensitive measure of disability in low-back pain.
        Spine. 1983; 8: 141-144
        • Roussel N.A.
        • Nijs J.
        • Meeus M.
        • Mylius V.
        • Fayt C.
        • Oostendorp R.
        Central sensitization and altered central pain processing in chronic low back pain: Fact or myth?.
        Clin J Pain. 2013; 29: 625-638
        • Schaible H.G.
        Peripheral and central mechanisms of pain generation.
        Handb Exp Pharmacol. 2007; : 3-28
        • Schey R.
        • Dickman R.
        • Parthasarathy S.
        • Quan S.F.
        • Wendel C.
        • Merchant J.
        • Powers J.
        • Han B.
        • Van Handel D.
        • Fass R.
        Sleep deprivation is hyperalgesic in patients with gastroesophageal reflux disease.
        Gastroenterology. 2007; 133: 1787-1795
        • Schilder A.
        • Hoheisel U.
        • Magerl W.
        • Benrath J.
        • Klein T.
        • Treede R.D.
        Sensory findings after stimulation of the thoracolumbar fascia with hypertonic saline suggest its contribution to low back pain.
        Pain. 2014; 155: 222-231
        • Schuh-Hofer S.
        • Wodarski R.
        • Pfau D.B.
        • Caspani O.
        • Magerl W.
        • Kennedy J.D.
        • Treede R.D.
        One night of total sleep deprivation promotes a state of generalized hyperalgesia: A surrogate pain model to study the relationship of insomnia and pain.
        Pain. 2013; 154: 1613-1621
        • Shochat T.
        • Aviram J.
        • Pud D.
        Longer sleep duration is related to increased pain sensitivity in healthy young men.
        Sleep Med. 2013; 14: e266
        • Sivertsen B.
        • Lallukka T.
        • Petrie K.J.
        • Steingrimsdottir O.A.
        • Stubhaug A.
        • Nielsen C.S.
        Sleep and pain sensitivity in adults.
        Pain. 2015; 156: 1433-1439
        • Smart K.M.
        • Blake C.
        • Staines A.
        • Doody C.
        Clinical indicators of ‘nociceptive’, ‘peripheral neuropathic’ and ‘central’ mechanisms of musculoskeletal pain. A Delphi survey of expert clinicians.
        Man Ther. 2010; 15: 80-87
        • Smith E.S.
        • Lewin G.R.
        Nociceptors: A phylogenetic view.
        J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2009; 195: 1089-1106
        • Smith M.T.
        • Edwards R.R.
        • McCann U.D.
        • Haythornthwaite J.A.
        The effects of sleep deprivation on pain inhibition and spontaneous pain in women.
        Sleep. 2007; 30: 494-505
        • Starkweather A.R.
        • Ramesh D.
        • Lyon D.E.
        • Siangphoe U.
        • Deng X.
        • Sturgill J.
        • Heineman A.
        • Elswick Jr, R.K.
        • Dorsey S.G.
        • Greenspan J.
        Acute low back pain: Differential somatosensory function and gene expression compared with healthy no-pain controls.
        Clin J Pain. 2016; 32: 933-939
        • Sterling M.
        Testing for sensory hypersensitivity or central hyperexcitability associated with cervical spine pain.
        J Manipulative Physiol Ther. 2008; 31: 534-539
        • Sterling M.
        • Jull G.
        • Vicenzino B.
        • Kenardy J.
        Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery.
        Pain. 2003; 104: 509-517
        • Strigo I.A.
        • Duncan G.H.
        • Boivin M.
        • Bushnell M.C.
        Differentiation of visceral and cutaneous pain in the human brain.
        J Neurophysiol. 2003; 89: 3294-3303
        • Takahashi K.
        • Taguchi T.
        • Itoh K.
        • Okada K.
        • Kawakita K.
        • Mizumura K.
        Influence of surface anesthesia on the pressure pain threshold measured with different-sized probes.
        Somatosens Mot Res. 2005; 22: 299-305
        • Tiede W.
        • Magerl W.
        • Baumgartner U.
        • Durrer B.
        • Ehlert U.
        • Treede R.D.
        Sleep restriction attenuates amplitudes and attentional modulation of pain-related evoked potentials, but augments pain ratings in healthy volunteers.
        Pain. 2010; 148: 36-42
        • van Wijk G.
        • Veldhuijzen D.S.
        Perspective on diffuse noxious inhibitory controls as a model of endogenous pain modulation in clinical pain syndromes.
        J Pain. 2010; 11: 408-419
        • Vos T.
        • Flaxman A.
        • Naghavi M.
        Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010 (vol 380, pg 2163, 2012).
        Lancet. 2014; 384: 582
        • Vuilleumier P.H.
        • Arguissain F.G.
        • Biurrun Manresa J.A.
        • Neziri A.Y.
        • Nirkko A.C.
        • Andersen O.K.
        • Arendt-Nielsen L.
        • Curatolo M.
        Psychophysical and electrophysiological evidence for enhanced pain facilitation and unaltered pain inhibition in acute low back pain patients.
        J Pain. 2017; 18: 1313-1323
        • Waddell G.
        • Newton M.
        • Henderson I.
        • Somerville D.
        • Main C.J.
        A Fear-Avoidance Beliefs Questionnaire (Fabq) and the role of fear-avoidance beliefs in chronic low-back-pain and disability.
        Pain. 1993; 52: 157-168
        • Willer J.C.
        • Lebars D.
        • Debroucker T.
        Diffuse noxious inhibitory controls in man—involvement of an opioidergic link.
        Eur J Pharmacol. 1990; 182: 347-355
        • Willer J.C.
        • Roby A.
        • Le Bars D.
        Psychophysical and electrophysiological approaches to the pain-relieving effects of heterotopic nociceptive stimuli.
        Brain. 1984; 107: 1095-1112
        • Woolf C.J.
        Evidence for a central component of post-injury pain hypersensitivity.
        Nature. 1983; 306: 686-688
        • Woolf C.J.
        • Costigan M.
        Transcriptional and posttranslational plasticity and the generation of inflammatory pain.
        Proc Natl Acad Sci U S A. 1999; 96: 7723-7730
        • Woolf C.J.
        • Salter M.W.
        Neuronal plasticity: Increasing the gain in pain.
        Science. 2000; 288: 1765-1769
        • Yarnitsky D.
        • Arendt-Nielsen L.
        • Bouhassira D.
        • Edwards R.R.
        • Fillingim R.B.
        • Granot M.
        • Hansson P.
        • Lautenbacher S.
        • Marchand S.
        • Wilder-Smith O.
        Recommendations on terminology and practice of psychophysical DNIC testing.
        Eur J Pain. 2010; 14: 339
        • Yarnitsky D.
        • Bouhassira D.
        • Drewes A.M.
        • Fillingim R.B.
        • Granot M.
        • Hansson P.
        • Landau R.
        • Marchand S.
        • Matre D.
        • Nilsen K.B.
        • Stubhaug A.
        • Treede R.D.
        • Wilder-Smith O.H.
        Recommendations on practice of conditioned pain modulation (CPM) testing.
        Eur J Pain. 2015; 19: 805-806
        • Yarnitsky D.
        • Crispel Y.
        • Eisenberg E.
        • Granovsky Y.
        • Ben-Nun A.
        • Sprecher E.
        • Best L.A.
        • Granot M.
        Prediction of chronic post-operative pain: Pre-operative DNIC testing identifies patients at risk.
        Pain. 2008; 138: 22-28
        • Yeung K.Y.
        • Ruzzo W.L.
        Principal component analysis for clustering gene expression data.
        Bioinformatics. 2001; 17: 763-774
        • Zale E.L.
        • Maisto S.A.
        • Ditre J.W.
        Interrelations between pain and alcohol: An integrative review.
        Clin Psychol Rev. 2015; 37: 57-71