Randomized, sham controlled trial of transcranial direct current stimulation for painful diabetic polyneuropathy

Yon Joon Kim, Jeonghun Ku, Hyun Jung Kim, Dal Jae Im, Hye Sun Lee, Kyung Ah Han, Youn Joo Kang, Yon Joon Kim, Jeonghun Ku, Hyun Jung Kim, Dal Jae Im, Hye Sun Lee, Kyung Ah Han, Youn Joo Kang

Abstract

Objective: To investigate the analgesic effect of transcranial direct current stimulation (tDCS) over the primary motor (M1), dorsolateral prefrontal cortex (DLPFC), and sham tDCS in patients with painful diabetic polyneuropathy (PDPN).

Methods: Patients with PDPN (n=60) were divided randomly into the three groups (n=20 per group). Each group received anodal tDCS with the anode centered over the left M1, DLPFC, or sham stimulation for 20 minutes at intensity of 2 mA for 5 consecutive days. A blinded physician rated the patients' pain using a visual analog scale (VAS), Clinical Global Impression (CGI) score, anxiety score, sleep quality, Beck Depression Inventory (BDI), and the pain threshold (PT) to pressure.

Results: After the tDCS sessions, the M1 group showed a significantly greater reduction in VAS for pain and PT versus the sham and DLPFC groups (p<0.001). The reduction in VAS for pain was sustained after 2 and 4 weeks of follow-up in the M1 group compared with the sham group (p<0.001, p=0.007). Significant differences were observed among the three groups over time in VAS for pain (p<0.001), CGI score (p=0.01), and PT (p<0.001). No significant difference was observed among the groups in sleep quality, anxiety score, or BDI score immediately after tDCS.

Conclusion: Five daily sessions of tDCS over the M1 can produce immediate pain relief, and relief 2- and 4-week in duration in patients with PDPN. Our findings provide the first evidence of a beneficial effect of tDCS on PDPN.

Keywords: Chronic pain; Diabetic neuropathy; Transcranial direct current stimulation.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Patient flow diagram. Twelve patients withdrew from the study: seven had early discharge during stimulation sessions and five withdrew after the third session of stimulation because of poor cooperation (n=4) or headache (n=1). PDPN, painful diabetic polyneuropathy; BDI, Beck Depression Index; MMSE, Mini-Mental State Examination; VAS, visual analog scale; PT, pain threshold; CGI, Clinical Global Impression; tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, dorsolateral prefrontal cortex.
Fig. 2
Fig. 2
Anodal tDCS. The anode was positioned over the M1 or DLPFC and the cathode over the contralateral supraorbital region (2 mA for 20 minutes on 5 consecutive days). tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, dorsolateral prefrontal cortex.
Fig. 3
Fig. 3
After 5 consecutive days of tDCS sessions over M1, pain reduction was significantly greater compared with the sham and DLPFC groups (***p<0.001) and compared with the sham group, its analgesic effect was sustained after 2 weeks (***p<0.001) and 4 weeks (**p<0.01) of follow-up. Likewise, the M1 group showed greater pain reduction than the DLPFC group (**p<0.01) after 2 weeks. tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, left dorsolateral prefrontal cortex; VAS, visual analog scale.
Fig. 4
Fig. 4
After 5 consecutive days of tDCS sessions, the M1 group exhibited a significantly greater reduction in CGI score (***p<0.001), which was decreased significantly after 2 and 4 weeks of follow-up compared with the sham group (*p=0.02, **p=0.008). CGI is rated on a 7-point scale: 1, normal, not ill at all; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; 7, most severely ill. tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, left dorsolateral prefrontal cortex; CGI, Clinical Global Impression.
Fig. 5
Fig. 5
After 5 consecutive days of tDCS sessions, the M1 group exhibited a significantly greater increase in pain threshold compared with the sham and DLPFC groups (***p<0.001). tDCS, transcranial direct current stimulation; M1, primary motor cortex; DLPFC, left dorsolateral prefrontal cortex.

References

    1. Boulton AJ, Malik RA, Arezzo JC, Sosenko JM. Diabetic somatic neuropathies. Diabetes Care. 2004;27:1458–1486.
    1. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006;29:1518–1522.
    1. Jensen MP, Chodroff MJ, Dworkin RH. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology. 2007;68:1178–1182.
    1. Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, et al. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005;352:341–350.
    1. Baron R. Mechanisms of disease: neuropathic pain: a clinical perspective. Nat Clin Pract Neurol. 2006;2:95–106.
    1. Fischer TZ, Waxman SG. Neuropathic pain in diabetes: evidence for a central mechanism. Nat Rev Neurol. 2010;6:462–466.
    1. Selvarajah D, Wilkinson ID, Emery CJ, Harris ND, Shaw PJ, Witte DR, et al. Early involvement of the spinal cord in diabetic peripheral neuropathy. Diabetes Care. 2006;29:2664–2669.
    1. Eaton SE, Harris ND, Rajbhandari SM, Greenwood P, Wilkinson ID, Ward JD, et al. Spinal-cord involvement in diabetic peripheral neuropathy. Lancet. 2001;358:35–36.
    1. Selvarajah D, Wilkinson ID, Emery CJ, Shaw PJ, Griffiths PD, Gandhi R, et al. Thalamic neuronal dysfunction and chronic sensorimotor distal symmetrical polyneuropathy in patients with type 1 diabetes mellitus. Diabetologia. 2008;51:2088–2092.
    1. Fischer TZ, Tan AM, Waxman SG. Thalamic neuron hyperexcitability and enlarged receptive fields in the STZ model of diabetic pain. Brain Res. 2009;1268:154–161.
    1. Fregni F, Freedman S, Pascual-Leone A. Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques. Lancet Neurol. 2007;6:188–191.
    1. Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006;117:845–850.
    1. Fregni F, Boggio PS, Lima MC, Ferreira MJ, Wagner T, Rigonatti SP, 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;122:197–209.
    1. Mori F, Codeca C, Kusayanagi H, Monteleone F, Buttari F, Fiore S, et al. Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis. J Pain. 2010;11:436–442.
    1. Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry. 2005;76:833–838.
    1. Fregni F, Boggio PS, Nitsche MA, Marcolin MA, Rigonatti SP, Pascual-Leone A. Treatment of major depression with transcranial direct current stimulation. Bipolar Disord. 2006;8:203–204.
    1. Boggio PS, Zaghi S, Lopes M, Fregni F. Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers. Eur J Neurol. 2008;15:1124–1130.
    1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33:S62–S69.
    1. Bastyr EJ, 3rd, Price KL, Bril V MBBQ Study Group. Development and validity testing of the neuropathy total symptom score-6: questionnaire for the study of sensory symptoms of diabetic peripheral neuropathy. Clin Ther. 2005;27:1278–1294.
    1. Fregni F, Gimenes R, Valle AC, Ferreira MJ, Rocha RR, Natalle L, 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;54:3988–3998.
    1. Roizenblatt S, Fregni F, Gimenez R, Wetzel T, Rigonatti SP, Tufik S, et al. Site-specific effects of transcranial direct current stimulation on sleep and pain in fibromyalgia: a randomized, sham-controlled study. Pain Pract. 2007;7:297–306.
    1. Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont) 2007;4:28–37.
    1. Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 1996;67:588–597.
    1. Rossi S, Cappa SF, Babiloni C, Pasqualetti P, Miniussi C, Carducci F, et al. Prefrontal [correction of Prefontal] cortex in long-term memory: an "interference" approach using magnetic stimulation. Nat Neurosci. 2001;4:948–952.
    1. Herwig U, Satrapi P, Schonfeldt-Lecuona C. Using the international 10-20 EEG system for positioning of transcranial magnetic stimulation. Brain Topogr. 2003;16:95–99.
    1. Reidler JS, Mendonca ME, Santana MB, Wang X, Lenkinski R, Motta AF, et al. Effects of motor cortex modulation and descending inhibitory systems on pain thresholds in healthy subjects. J Pain. 2012;13:450–458.
    1. Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007;72:208–214.
    1. Rasche D, Ruppolt M, Stippich C, Unterberg A, Tronnier VM. Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience. Pain. 2006;121:43–52.
    1. Shin HC, Chapin JK. Mapping the effects of motor cortex stimulation on somatosensory relay neurons in the rat thalamus: direct responses and afferent modulation. Brain Res Bull. 1990;24:257–265.
    1. Yoo WK, You SH, Ko MH, Kim ST, Park CH, Park JW, et al. High frequency rTMS modulation of the sensorimotor networks: behavioral changes and fMRI correlates. Neuroimage. 2008;39:1886–1895.
    1. Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology. 2001;57:1899–1901.
    1. Lang N, Siebner HR, Ward NS, Lee L, Nitsche MA, Paulus W, et al. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain? Eur J Neurosci. 2005;22:495–504.
    1. Lefaucheur JP, Drouot X, Keravel Y, Nguyen JP. Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex. Neuroreport. 2001;12:2963–2965.
    1. Antal A, Kriener N, Lang N, Boros K, Paulus W. Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine. Cephalalgia. 2011;31:820–828.
    1. Grundmann L, Rolke R, Nitsche MA, Pavlakovic G, Happe S, Treede RD, et al. Effects of transcranial direct current stimulation of the primary sensory cortex on somatosensory perception. Brain Stimul. 2011;4:253–260.
    1. Arendt-Nielsen L, Bjerring P. Sensory and pain threshold characteristics to laser stimuli. J Neurol Neurosurg Psychiatry. 1988;51:35–42.

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