Bayesian analysis of the effect of transcranial direct current stimulation on experimental pain sensitivity in older adults with knee osteoarthritis: randomized sham-controlled pilot clinical study

Hyochol Ahn, Robert Suchting, Adam J Woods, Hongyu Miao, Charles Green, Raymond Y Cho, Eunyoung Choi, Roger B Fillingim, Hyochol Ahn, Robert Suchting, Adam J Woods, Hongyu Miao, Charles Green, Raymond Y Cho, Eunyoung Choi, Roger B Fillingim

Abstract

Purpose: Previous studies have indicated that transcranial direct current stimulation (tDCS) with the anode over the motor cortex and the cathode over the contralateral supraorbital region is effective in reducing clinical pain in patients with chronic pain, but these studies have not focused on experimental pain sensitivity. Therefore, the aim of this study was to examine the effect of tDCS on experimental pain sensitivity in older adults with knee osteoarthritis (OA).

Patients and methods: Forty community-dwelling participants aged 50-70 years with knee OA pain were randomly assigned to receive five daily sessions of 2 mA tDCS for 20 minutes (n = 20) or sham tDCS (n = 20) using a parallel group design. A multimodal quantitative sensory testing battery was completed, including heat pain, pressure pain threshold (PPT), punctate mechanical pain, and conditioned pain modulation (CPM).

Results: The active tDCS group showed greater increases in heat pain thresholds and tolerances, PPTs, and CPM, and reductions in punctate pain. In addition, beneficial changes in experimental pain measures were associated with reductions in clinical pain. Future studies are needed to extend these findings to better understand the underlying mechanisms of tDCS as well as to optimize treatment parameters including number and duration of stimulation sessions.

Conclusion: Our findings demonstrate that tDCS reduces experimental pain sensitivity, and these beneficial changes in experimental pain measures were associated with reductions in clinical pain.

Keywords: Bayesian analysis; knee osteoarthritis; quantitative sensory testing; transcranial direct current stimulation.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Interpretation of posterior distribution of the effect of tDCS group on heat pain threshold. Abbreviations: CrI, credible interval; tDCS, transcranial direct current stimulation.

References

    1. Hunter DJ, Mcdougall JJ, Keefe FJ. The symptoms of osteoarthritis and the genesis of pain. Rheum Dis Clin North Am. 2008;34(3):623–643.
    1. Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58(1):26–35.
    1. Institute of Medicine . Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: National Academies Press; 2011.
    1. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10(9):895–926.
    1. Finan PH, Buenaver LF, Bounds SC, et al. Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis Rheum. 2013;65(2):363–372.
    1. Rakel B, Vance C, Zimmerman MB, Petsas-Blodgett N, Amendola A, Sluka KA. Mechanical hyperalgesia and reduced quality of life occur in people with mild knee osteoarthritis pain. Clin J Pain. 2015;31(4):315–322.
    1. Neogi T, Guermazi A, Roemer F, et al. Association of Joint Inflammation With Pain Sensitization in Knee Osteoarthritis: The Multicenter Osteoarthritis Study. Arthritis Rheumatol. 2016;68(3):654–661.
    1. Gwilym SE, Keltner JR, Warnaby CE, et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 2009;61(9):1226–1234.
    1. Hiramatsu T, Nakanishi K, Yoshimura S, et al. The dorsolateral prefrontal network is involved in pain perception in knee osteoarthritis patients. Neurosci Lett. 2014;581:109–114.
    1. Sofat N, Smee C, Hermansson M, et al. Functional MRI demonstrates pain perception in hand osteoarthritis has features of central pain processing. J Biomed Graph Comput. 2013;3(4)
    1. Fregni F, Gimenes R, Valle AC, et al. A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum. 2006;54(12):3988–3998.
    1. Simis M, Reidler JS, Duarte Macea D, et al. Investigation of central nervous system dysfunction in chronic pelvic pain using magnetic resonance spectroscopy and noninvasive brain stimulation. Pain Pract. 2015;15(5):423–432.
    1. Mori F, Codecà C, Kusayanagi H, et al. Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. J Pain. 2010;11(5):436–442.
    1. Antal A, Terney D, Kühnl S, Paulus W. Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition. J Pain Symptom Manage. 2010;39(5):890–903.
    1. Nitsche MA, Cohen LG, Wassermann EM, et al. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008;1(3):206–223.
    1. Bikson M, Grossman P, Thomas C, et al. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016;9(5):641–661.
    1. Woods AJ, Antal A, Bikson M, et al. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin Neurophysiol. 2016;127(2):1031–1048.
    1. Suokas AK, Walsh DA, Mcwilliams DF, et al. Quantitative sensory testing in painful osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2012;20(10):1075–1085.
    1. Arendt-Nielsen L, Skou ST, Nielsen TA, Petersen KK. Altered Central Sensitization and Pain Modulation in the CNS in Chronic Joint Pain. Curr Osteoporos Rep. 2015;13(4):225–234.
    1. Fregni F, Boggio PS, Lima MC, et al. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain. 2006;122(1–2):197–209.
    1. Ahn H, Woods AJ, Kunik ME, et al. Efficacy of transcranial direct current stimulation over primary motor cortex (anode) and contralateral supraorbital area (cathode) on clinical pain severity and mobility performance in persons with knee osteoarthritis: An experimenter- and participant-blinded, randomized, sham-controlled pilot clinical study. Brain Stimul. 2017;10(5):902–909.
    1. Mylius V, Borckardt JJ, Lefaucheur JP. Noninvasive cortical modulation of experimental pain. Pain. 2012;153(7):1350–1363.
    1. Altman R, Alarcón G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum. 1991;34(5):505–514.
    1. Lefaucheur JP, Antal A, Ayache SS, et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) Clin Neurophysiol. 2017;128(1):56–92.
    1. Fregni F, Pascual-Leone A. Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol. 2007;3(7):383–393.
    1. Valle A, Roizenblatt S, Botte S, et al. Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial. J Pain Manag. 2009;2(3):353–361.
    1. Luedtke K, Rushton A, Wright C, Geiss B, Juergens TP, May A. Transcranial direct current stimulation for the reduction of clinical and experimentally induced pain: a systematic review and meta-analysis. Clin J Pain. 2012;28(5):452–461.
    1. O’Connell NE, Wand BM, Marston L, Spencer S, Desouza LH. Noninvasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2014;4:CD008208.
    1. Gandiga PC, Hummel FC, Cohen LG. Stimulation TDC. Transcranial DC stimulation (tDCS): A tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006;117(4):845–850.
    1. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15(12):1833–1840.
    1. Seror R, Tubach F, Baron G, et al. Individualising the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) function subscale: incorporating patient priorities for improvement to measure functional impairment in hip or knee osteoarthritis. Ann Rheum Dis. 2008;67(4):494–499.
    1. Yang KG, Raijmakers NJ, Verbout AJ, Dhert WJ, Saris DB. Validation of the short-form WOMAC function scale for the evaluation of osteoarthritis of the knee. J Bone Joint Surg Br. 2007;89(1):50–56.
    1. King CD, Sibille KT, Goodin BR, et al. Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis. Osteoarthritis Cartilage. 2013;21(9):1243–1252.
    1. Pocock SJ, Assmann SE, Enos LE, Kasten LE. Subgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practice and problems. Stat Med. 2002;21(19):2917–2930.
    1. Gelman A, Hill J. Data Analysis Using Regression and Multilevel/ hierarchical Models. New York: Cambridge University Press; 2007.
    1. Schmitz JM, Green CE, Hasan KM, et al. PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double-blind randomized controlled pilot trial. Addiction. 2017;112(10):1861–1868.
    1. NCT02271919 [homepage on the Internet] Varenicline and Combined Nicotine Replacement Therapy (NRT) for Smoking Cessation. [Accessed September 14, 2017]. Available from: .
    1. NCT02556606 [homepage on the Internet] Ketamine for Treatment Resistant Late-Life Depression. [Accessed September 14, 2017]. Available from: .
    1. NCT01535573 [homepage on the Internet] Citalopram for Cocaine Dependence. [Accessed September 14, 2017]. Available from: .
    1. NCT02162849 [homepage on the Internet] Reward Sensitivity and Pharmacotherapy for Smoking Cessation. [Accessed September 14, 2017]. Available from: .
    1. Johnson VE. Revised standards for statistical evidence. Proc Natl Acad Sci USA. 2013;110(48):19313–19317.
    1. Gelman A. The Failure of Null Hypothesis Significance Testing When Studying Incremental Changes, and What to Do About It. Pers Soc Psychol Bull. 2018;44(1):16–23.
    1. Bürkner P-C. An R Package for Bayesian Multilevel Models Using Stan. J Stat Softw. 2017;80(1):1–28.
    1. Chang WJ, Bennell KL, Hodges PW, et al. Addition of transcranial direct current stimulation to quadriceps strengthening exercise in knee osteoarthritis: A pilot randomised controlled trial. PLoS One. 2017;12(6):e0180328.
    1. Moloney TM, Witney AG. Pressure pain thresholds increase after preconditioning 1 Hz repetitive transcranial magnetic stimulation with transcranial direct current stimulation. PLoS One. 2014;9(3):e92540.
    1. Bachmann CG, Muschinsky S, Nitsche MA, et al. Transcranial direct current stimulation of the motor cortex induces distinct changes in thermal and mechanical sensory percepts. Clin Neurophysiol. 2010;121(12):2083–2089.
    1. Ihle K, Rodriguez-Raecke R, Luedtke K, May A. tDCS modulates cortical nociceptive processing but has little to no impact on pain perception. Pain. 2014;155(10):2080–2087.
    1. Knotkova H, Woods AJ, Bikson M, Nitsche M. Transcranial direct current stimulation (tDCS): What pain practitioners need to know. Prac Pain Manag. 2015;15:58–66.
    1. Nitsche MA, Grundey J, Liebetanz D, Lang N, Tergau F, Paulus W. Catecholaminergic consolidation of motor cortical neuroplasticity in humans. Cereb Cortex. 2004;14(11):1240–1245.
    1. Nitsche MA, Jaussi W, Liebetanz D, Lang N, Tergau F, Paulus W. Consolidation of human motor cortical neuroplasticity by D-cycloserine. Neuropsychopharmacology. 2004;29(8):1573–1578.
    1. Nitsche MA, Liebetanz D, Schlitterlau A, et al. GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans. Eur J Neurosci. 2004;19(10):2720–2726.
    1. Nitsche MA, Lampe C, Antal A, et al. Dopaminergic modulation of long-lasting direct current-induced cortical excitability changes in the human motor cortex. Eur J Neurosci. 2006;23(6):1651–1657.
    1. Nitsche MA, Kuo MF, Karrasch R, Wächter B, Liebetanz D, Paulus W. Serotonin affects transcranial direct current-induced neuroplasticity in humans. Biol Psychiatry. 2009;66(5):503–508.
    1. Stagg CJ, Lin RL, Mezue M, et al. Widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex. J Neurosci. 2013;33(28):11425–11431.
    1. Peyron R, Laurent B, García-Larrea L. Functional imaging of brain responses to pain. A review and meta-analysis (2000) Neurophysiol Clin. 2000;30(5):263–288.
    1. Peyron R, Faillenot I, Mertens P, Laurent B, Garcia-Larrea L. Motor cortex stimulation in neuropathic pain. Correlations between analgesic effect and hemodynamic changes in the brain. A PET study. Neuroimage. 2007;34(1):310–321.
    1. Polanía R, Paulus W, Nitsche MA. Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation. Hum Brain Mapp. 2012;33(10):2499–2508.
    1. Dasilva AF, Mendonca ME, Zaghi S, et al. tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine. Headache. 2012;52(8):1283–1295.
    1. Garcia-Larrea L, Peyron R. Motor cortex stimulation for neuropathic pain: From phenomenology to mechanisms. Neuroimage. 2007;37(Suppl 1):S71–S79.
    1. DosSantos MF, Love TM, Martikainen IK, et al. Immediate effects of tDCS on the µ-opioid system of a chronic pain patient. Front Psychiatry. 2012;3:93.
    1. Maihöfner C, Handwerker HO, Neundörfer B, Birklein F. Cortical reorganization during recovery from complex regional pain syndrome. Neurology. 2004;63(4):693–701.
    1. Pleger B, Tegenthoff M, Ragert P, et al. Sensorimotor retuning [corrected] in complex regional pain syndrome parallels pain reduction. Ann Neurol. 2005;57(3):425–429.
    1. Gelman A. Prior distributions for variance parameters in hierarchical models. Bayesian Analysis. 2006;1(3):515–533.
    1. Mcneish D. On Using Bayesian Methods to Address Small Sample Problems. Structural Equation Modeling: A Multidisciplinary Journal. 2016;23(5):750–773.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever