Abstract
Chronic low back pain (CLBP) is highly disabling, but often without identifiable source.
Focus has been on impaired anti-nociceptive mechanisms contributing to pain maintenance,
though methods of targeting this impairment remain limited. This randomised-controlled
cross-over pilot trial used active versus sham medial prefrontal cortex (mPFC) high-definition
transcranial direct current stimulation (HD-tDCS) for 3-consecutive days to improve
descending pain inhibitory function. Twelve CLBP patients were included with an average
visual analogue scale (VAS) pain intensity of 3.0 ± 1.5 and pain duration of 5.3 ±
2.6 years. Pressure pain thresholds (PPTs), conditioned pain modulation (CPM), and
temporal summation of pain (TSP) assessed by cuff algometry, as well as pain symptomatology
(intensity, unpleasantness, quality, disability) and related psychological features
(pain catastrophizing, anxiety, affect), were assessed on Day1 before 3 consecutive
days of HD-tDCS sessions (each 20 minutes), at 24-hours (Day 4) and 2-weeks (Day 21)
following final HD-tDCS. Blinding was successful. No significant differences in psychophysical
(PPT, CPM, TSP), symptomatology or psychological outcomes were observed between active
and sham HD-tDCS on Day4 and Day21. CPM-effects at Day 1 negatively correlated with
change in CPM-effect at Day4 following active HD-tDCS (P = .002). Lack of efficacy was attributed to several factors, not least that patients
did not display impaired CPM at baseline.
Trial registration
: ClinicalTrials.gov (NCT03864822).
Perspective
Medial prefrontal HD-tDCS did not alter pain, psychological nor psychophysical outcomes,
though correlational analysis suggested response may depend on baseline pain inhibitory
efficacy, with best potential effects in patients with severe impairments in descending
pain inhibitory mechanisms. Future work should focus on appropriate patient selection
and optimising stimulation targeting.
Key words
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References
- Is transcranial direct current stimulation (tDCS) effective for chronic low back pain? A systematic review and meta-analysis.J Neural Transm (Vienna). 2020; 127: 1257-1270https://doi.org/10.1007/s00702-020-02223-w
- The RESOLVE trial for people with chronic low back pain: protocol for a randomised clinical trial.J Physiother. 2017; 63: 47-48https://doi.org/10.1016/j.jphys.2016.11.001
- Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain.J Neurosci. 2006; 26: 12165-12173https://doi.org/10.1523/JNEUROSCI.3576-06.2006
- Central nervous system targets: supraspinal mechanisms of analgesia.Neurotherapeutics. 2020; https://doi.org/10.1007/s13311-020-00887-6
- Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care.Behav Res Ther. 1997; 35: 785-791https://doi.org/10.1016/s0005-7967(97)00025-9
- Proposal of a new transcranial direct current stimulation safety screening tool.Am J Phys Med Rehabil. 2019; 98: e77-e78https://doi.org/10.1097/PHM.0000000000001096
- The accuracy of pain and fatigue items across different reporting periods.Pain. 2008; 139: 146-157https://doi.org/10.1016/j.pain.2008.03.024
- Optimised transcranial direct current stimulation (tDCS) for fibromyalgia-targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol.BMJ Open. 2019; 9e032710https://doi.org/10.1136/bmjopen-2019-032710
- Intrinsic functional connectivity of periaqueductal gray subregions in humans.Hum Brain Mapp. 2016; 37: 1514-1530https://doi.org/10.1002/hbm.23117
- International physical activity questionnaire: 12-country reliability and validity.Med Sci Sports Exerc. 2003; 35: 1381-1395https://doi.org/10.1249/01.MSS.0000078924.61453.FB
- The positive and negative affect schedule (PANAS): construct validity, measurement properties and normative data in a large non-clinical sample.Br J Clin Psychol. 2004; 43: 245-265https://doi.org/10.1348/0144665031752934
- Activation of the descending pain modulatory system using cuff pressure algometry: Back translation from man to rat.Eur J Pain. 2020; 24: 1330-1338https://doi.org/10.1002/ejp.1580
- Electrode positioning and montage in transcranial direct current stimulation.J Vis Exp. 2011; https://doi.org/10.3791/2744
- Differentiating trait pain from state pain: A window into brain mechanisms underlying how we experience and cope with pain.Pain Rep. 2019; 4: e735https://doi.org/10.1097/PR9.0000000000000735
- Pain mechanisms in low back pain: A systematic review with meta-analysis of mechanical quantitative sensory testing outcomes in people with nonspecific low back pain.J Orthop Sports Phys Ther. 2019; 49: 698-715https://doi.org/10.2519/jospt.2019.8876
- Supraspinal opioid circuits differentially modulate spinal neuronal responses in neuropathic rats.Anesthesiology. 2020; 132: 881-894https://doi.org/10.1097/ALN.0000000000003120
- Chronic low back pain and the risk of depression or anxiety symptoms: Insights from a longitudinal twin study.Spine J. 2017; 17: 905-912https://doi.org/10.1016/j.spinee.2017.02.009
- High-definition transcranial direct current stimulation enhances conditioned pain modulation in healthy volunteers: A randomized trial.J Pain. 2016; 17: 600-605https://doi.org/10.1016/j.jpain.2016.01.472
- painDETECT: A new screening questionnaire to identify neuropathic components in patients with back pain.Curr Med Res Opin. 2006; 22: 1911-1920https://doi.org/10.1185/030079906X132488
- Validating a sham condition for use in high definition transcranial direct current stimulation.Brain Stimul. 2015; 8: 551-554https://doi.org/10.1016/j.brs.2015.01.399
- Chronic widespread back pain is distinct from chronic local back pain.Clin J Pain. 2016; 32: 568-579https://doi.org/10.1097/AJP.0000000000000300
- Conditioned pain modulation in patients with nonspecific chronic back pain with chronic local pain, chronic widespread pain, and fibromyalgia.Pain. 2017; 158: 430-439https://doi.org/10.1097/j.pain.0000000000000777
- Differences in pain processing between patients with chronic low back pain, recurrent low back pain, and fibromyalgia.Pain Physician. 2017; 20: 307-318
- Arendt-Nielsen L: User-independent assessment of conditioning pain modulation by cuff pressure algometry.Eur J Pain. 2017; 21: 552-561https://doi.org/10.1002/ejp.958
- Assessment of musculoskeletal pain sensitivity and temporal summation by cuff pressure algometry: A reliability study.Pain. 2015; 156: 2193-2202https://doi.org/10.1097/j.pain.0000000000000294
- What low back pain is and why we need to pay attention.Lancet. 2018; 391: 2356-2367https://doi.org/10.1016/S0140-6736(18)30480-X
- Treating low back pain with combined cerebral and peripheral electrical stimulation: A randomized, double-blind, factorial clinical trial.Eur J Pain. 2017; 21: 1132-1143https://doi.org/10.1002/ejp.1037
- Inventory of personal factors influencing conditioned pain modulation in healthy people: A systematic literature review.Pain Pract. 2016; 16: 758-769https://doi.org/10.1111/papr.12305
- Subgrouping low back pain: A comparison of the STarT Back Tool with the Orebro Musculoskeletal Pain Screening Questionnaire.Eur J Pain. 2010; 14: 83-89https://doi.org/10.1016/j.ejpain.2009.01.003
- Effects of repeated conditioning pain modulation in healthy volunteers.Eur J Pain. 2018; 22: 1833-1843https://doi.org/10.1002/ejp.1279
- Are current blinding methods for transcranial direct current stimulation (tDCS) effective in healthy populations?.Clin Neurophysiol. 2015; 126: 2045-2046https://doi.org/10.1016/j.clinph.2015.04.001
- Transcranial direct current stimulation: Five important issues we aren't discussing (but probably should be).Front Syst Neurosci. 2014; 8: 2https://doi.org/10.3389/fnsys.2014.00002
- Measuring the global burden of low back pain.Best Pract Res Clin Rheumatol. 2010; 24: 155-165https://doi.org/10.1016/j.berh.2009.11.002
- Measures of anxiety: State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A).Arthritis Care Res (Hoboken). 2011; 63: S467-S472https://doi.org/10.1002/acr.20561
- Transcranial magnetic stimulation (TMS) of the sensorimotor cortex and medial frontal cortex modifies human pain perception.Clin Neurophysiol. 2003; 114: 860-866https://doi.org/10.1016/s1388-2457(03)00034-8
- Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks.Proc Natl Acad Sci U S A. 2013; 110: 18692-18697https://doi.org/10.1073/pnas.1312902110
- The medial prefrontal cortex as a central hub for mental comorbidities associated with chronic pain.Int J Mol Sci. 2020; 21https://doi.org/10.3390/ijms21103440
- The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies.Front Cell Neurosci. 2015; 9: 181https://doi.org/10.3389/fncel.2015.00181
- The face scale: A brief, nonverbal method for assessing patient mood.Arthritis Rheum. 1986; 29: 906-909https://doi.org/10.1002/art.1780290714
- No effect of a single session of transcranial direct current stimulation on experimentally induced pain in patients with chronic low back pain–an exploratory study.PLoS One. 2012; 7: e48857https://doi.org/10.1371/journal.pone.0048857
- The human pain system exhibits higher-order plasticity (metaplasticity).Neurobiol Learn Mem. 2018; 154: 112-120https://doi.org/10.1016/j.nlm.2018.04.003
- Reliability and validity of the back performance scale: Observing activity limitation in patients with back pain.Spine (Phila Pa 1976). 2004; 29: 903-907https://doi.org/10.1097/00007632-200404150-00017
- Non-specific low back pain.Lancet. 2017; 389: 736-747https://doi.org/10.1016/S0140-6736(16)30970-9
- Transcranial direct current stimulation for affective symptoms and functioning in chronic low back pain: A pilot double-blinded, randomized, placebo-controlled trial.Pain Med. 2019; 20: 1166-1177https://doi.org/10.1093/pm/pny188
- Transcranial Direct Current Stimulation (tDCS) targeting left dorsolateral prefrontal cortex modulates task-induced acute pain in healthy volunteers.Pain Med. 2016; 17: 737-745https://doi.org/10.1093/pm/pnv042
- Effects of transcranial direct current stimulation (tDCS) on pain distress tolerance: A preliminary study.Pain Med. 2015; 16: 1580-1588https://doi.org/10.1111/pme.12798
- Comorbidity of chronic back pain and depression in Germany: Results from the GEDA study, 2009 and 2010.Z Evid Fortbild Qual Gesundhwes. 2018; 137-138: 62-68https://doi.org/10.1016/j.zefq.2018.10.003
- Adverse events of tDCS and tACS: A review.Clin Neurophysiol Pract. 2017; 2: 19-25https://doi.org/10.1016/j.cnp.2016.12.003
- Attenuation of cortical activity triggering descending pain inhibition in chronic low back pain patients: A functional magnetic resonance imaging study.J Anesth. 2017; 31: 523-530https://doi.org/10.1007/s00540-017-2343-1
- Alterations in temporal summation of pain and conditioned pain modulation across an episode of experimental exercise-induced low back pain.J Pain. 2019; 20: 264-276https://doi.org/10.1016/j.jpain.2018.08.010
- Recurrent low back pain patients demonstrate facilitated pronociceptive mechanisms when in pain, and impaired antinociceptive mechanisms with and without pain.Pain. 2019; 160: 2866-2876https://doi.org/10.1097/j.pain.0000000000001679
- Alterations in pro-nociceptive and anti-nociceptive mechanisms in patients with low back pain: A systematic review with meta-analysis.Pain. 2019; https://doi.org/10.1097/j.pain.0000000000001737
- Alterations in pronociceptive and antinociceptive mechanisms in patients with low back pain: A systematic review with meta-analysis.Pain. 2020; 161: 464-475https://doi.org/10.1097/j.pain.0000000000001737
- The McGill Pain Questionnaire: Major properties and scoring methods.Pain. 1975; 1: 277-299https://doi.org/10.1016/0304-3959(75)90044-5
- Comparison of five conditioned pain modulation paradigms and influencing personal factors in healthy adults.Eur J Pain. 2020; https://doi.org/10.1002/ejp.1665
- The longitudinal relationships between pain severity and disability versus health-related quality of life and costs among chronic low back pain patients.Qual Life Res. 2020; 29: 275-287https://doi.org/10.1007/s11136-019-02302-w
- Polarity-specific modulation of pain processing by transcranial direct current stimulation - A blinded longitudinal fMRI study.J Headache Pain. 2018; 19: 99https://doi.org/10.1186/s10194-018-0924-5
- Polarity-independent effects of transcranial direct current stimulation over the bilateral opercular somatosensory region: A magnetoencephalography study.Neuroreport. 2017; 28: 838-844https://doi.org/10.1097/WNR.0000000000000845
- Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain.J Neurosci. 2015; 35: 7264-7271https://doi.org/10.1523/JNEUROSCI.3862-14.2015
- Cathodal and anodal left prefrontal tDCS and the perception of control over pain.Clin J Pain. 2014; 30: 693-700https://doi.org/10.1097/AJP.0000000000000025
- Sensitivity and sensitisation in relation to pain severity in knee osteoarthritis: Trait or state?.Ann Rheum Dis. 2015; 74: 682-688https://doi.org/10.1136/annrheumdis-2013-204191
- Pre-stimulus brain activity is associated with state-anxiety changes during single-session transcranial direct current stimulation.Front Hum Neurosci. 2019; 13: 266https://doi.org/10.3389/fnhum.2019.00266
- Transcranial direct current stimulation of the motor cortex in the treatment of chronic nonspecific low back pain: A randomized, double-blind exploratory study.Clin J Pain. 2013; 29: 26-34https://doi.org/10.1097/AJP.0b013e318247ec09
- Rethinking clinical trials of transcranial direct current stimulation: participant and assessor blinding is inadequate at intensities of 2mA.PLoS One. 2012; 7: e47514https://doi.org/10.1371/journal.pone.0047514
- Non-invasive brain stimulation techniques for chronic pain.Cochrane Database Syst Rev. 2018; 3CD008208https://doi.org/10.1002/14651858.CD008208.pub4
- Low pressure pain thresholds are associated with, but does not predispose for, low back pain.Eur Spine J. 2011; 20: 2120-2125https://doi.org/10.1007/s00586-011-1796-4
- Topographic mapping of pain sensitivity of the lower back - a comparison of healthy controls and patients with chronic non-specific low back pain.Scand J Pain. 2019; 19: 25-37https://doi.org/10.1515/sjpain-2018-0113
- Role of the prefrontal cortex in pain processing.Mol Neurobiol. 2019; 56: 1137-1166https://doi.org/10.1007/s12035-018-1130-9
- Transcranial direct current stimulation as a therapeutic tool for chronic pain.J ECT. 2018; 34: e36-e50https://doi.org/10.1097/YCT.0000000000000518
- Pain affect encoded in human anterior cingulate but not somatosensory cortex.Science. 1997; 277: 968-971https://doi.org/10.1126/science.277.5328.968
- Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps.Brain Stimul. 2018; 11: 991-997https://doi.org/10.1016/j.brs.2018.04.022
- Toward development of sham protocols for high-definition transcranial direct current stimulation (HD-tDCS).NeuroRegulation. 2014; 1 (62-62)
- 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 (Phila Pa 1976). 1983; 8: 141-144https://doi.org/10.1097/00007632-198303000-00004
- Central sensitization and altered central pain processing in chronic low back pain: Fact or myth?.Clin J Pain. 2013; 29: 625-638https://doi.org/10.1097/AJP.0b013e31826f9a71
- Pressure pain thresholds fluctuate with, but do not usefully predict, the clinical course of painful temporomandibular disorder.Pain. 2014; 155: 2134-2143https://doi.org/10.1016/j.pain.2014.08.007
- Manual for the State-Trait Anxiety Inventory.Palo Alto, CA1983
- Back Performance Scale for the assessment of mobility-related activities in people with back pain.Phys Ther. 2002; 82: 1213-1223
- The pain catastrophizing scale: Development and validation.Psychol Assess. 1995; 7: 524
- Field modeling for transcranial magnetic stimulation: A useful tool to understand the physiological effects of TMS?.Conf Proc IEEE Eng Med Biol Soc. 2015; 2015: 222-225https://doi.org/10.1109/EMBC.2015.7318340
- Exploring the effects of anodal and cathodal high definition transcranial direct current stimulation targeting the dorsal anterior cingulate cortex.Sci Rep. 2018; 8: 4454https://doi.org/10.1038/s41598-018-22730-x
- Abnormal medial prefrontal cortex functional connectivity and its association with clinical symptoms in chronic low back pain.Pain. 2019; 160: 1308-1318https://doi.org/10.1097/j.pain.0000000000001507
- Differential effects of cathodal transcranial direct current stimulation of prefrontal, motor and somatosensory cortices on cortical excitability and pain perception - A double-blind randomised sham-controlled study.Eur J Neurosci. 2015; 42: 2426-2437https://doi.org/10.1111/ejn.13043
- Efficacy of classification-based cognitive functional therapy in patients with non-specific chronic low back pain: A randomized controlled trial.Eur J Pain. 2013; 17: 916-928https://doi.org/10.1002/j.1532-2149.2012.00252.x
- Technique and considerations in the use of 4x1 ring high-definition transcranial direct current stimulation (HD-tDCS).J Vis Exp. 2013; : e50309https://doi.org/10.3791/50309
- Focal modulation of the primary motor cortex in fibromyalgia using 4x1-ring high-definition transcranial direct current stimulation (HD-tDCS): Immediate and delayed analgesic effects of cathodal and anodal stimulation.J Pain. 2013; 14: 371-383https://doi.org/10.1016/j.jpain.2012.12.007
- Supraspinal pain processing: Distinct roles of emotion and attention.Neuroscientist. 2010; 16: 276-284https://doi.org/10.1177/1073858409359200
- Reliability of pressure pain threshold testing in healthy pain free young adults.Scand J Pain. 2015; 9: 38-41https://doi.org/10.1016/j.sjpain.2015.05.004
- Development and validation of brief measures of positive and negative affect: The PANAS scales.J Pers Soc Psychol. 1988; 54: 1063-1070https://doi.org/10.1037//0022-3514.54.6.1063
- Global low back pain prevalence and years lived with disability from 1990 to 2017: Estimates from the Global Burden of Disease Study 2017.Ann Transl Med. 2020; 8: 299https://doi.org/10.21037/atm.2020.02.175
- Disrupted functional connectivity of the periaqueductal gray in chronic low back pain.Neuroimage Clin. 2014; 6: 100-108https://doi.org/10.1016/j.nicl.2014.08.019
- Impaired mesocorticolimbic connectivity underlies increased pain sensitivity in chronic low back pain.Neuroimage. 2020; 218116969https://doi.org/10.1016/j.neuroimage.2020.116969
- Modulation of cold pain perception by transcranial direct current stimulation in healthy individuals.Neuromodulation. 2013; 16 (discussion 348): 345-348https://doi.org/10.1111/ner.12009
- Anterior cingulate cortex contributes to the descending facilitatory modulation of pain via dorsal reticular nucleus.Eur J Neurosci. 2005; 22: 1141-1148https://doi.org/10.1111/j.1460-9568.2005.04302.x
- Evaluating cortical alterations in patients with chronic back pain using neuroimaging techniques: Recent advances and perspectives.Front Psychol. 2019; 10: 2527https://doi.org/10.3389/fpsyg.2019.02527
Article info
Publication history
Published online: March 03, 2021
Accepted:
February 19,
2021
Received in revised form:
February 9,
2021
Received:
October 14,
2020
Footnotes
Center for Neuroplasticity and Pain (CNAP) is supported by the Danish National Research Foundation (DNRF121). Nocitech is partly owned by Aalborg University.
The authors have no conflicts of interest to declare.
Trial registration: ClinicalTrials.gov (NCT03864822).
Identification
Copyright
© 2021 by United States Association for the Study of Pain, Inc.