The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment

Abstract

Background : Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients. Methods : Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group ( n = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group ( n = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS ( n = 12) and sham ts-DCS ( n = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level. Results : Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline. Conclusions : Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception. Clinical Trial Registration: www.ClinicalTrials.gov , identifier #NCT02331654.

Beyond rehabilitation in MS: Insights from non-invasive brain stimulation

“…Furthermore, task-related functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para-)cingulate increased significantly only after real rTMS. 39 Other symptoms Few data are available on application of NIBS for the treatment of other MS-related symptoms, such as pain, 40,41 sensory deficits, 42 lower urinary tract dysfunction, 43 and dysphagia. 44 In 19 patients with RRMS with chronic neuropathic pain, anodal tDCS over the motor cortex contralateral to the painful body region for 5 consecutive days was associated with significantly greater pain improvement compared with sham, lasting up to 3 weeks.…”

No Immediate Effects of Transcranial Direct Current Stimulation at Various Intensities on Cerebral Blood Flow in People with Multiple Sclerosis

“…Because some MS symptoms (e.g., neuropathic pain) are treatment-resistant [2], practical and inexpensive adjunctive therapies, like transcranial direct current stimulation (tDCS), are of high interest. Despite promising findings in tDCS studies in people with multiple sclerosis (PwMS) [3][4][5] (see [6] for a review), the validity and utility of tDCS is under scrutiny. For example, a critical review [7] did not support the idea that tDCS has a reliable neurophysiological effect beyond motor evoked potential (MEP) amplitude modulation.…”

Non-invasive Brain and Spinal Stimulation for Pain and Related Symptoms in Multiple Sclerosis: A Systematic Review

“…We found two studies (Table 3), one dealing with tRNS (Palm et al, 2016) and one with tsDCS (Berra et al, 2019). Palm et al (2016) explored the effect of tRNS over the left DLPFC on affective symptoms, attention, fatigue, and pain by exploring pain perception and attentional resources in a prospective randomized, cross-over, sham-controlled study of sixteen MS patients with neuropathic pain.…”

“…New NIBSS protocol have been recently introduced in the clinical setting, including tRNS (Terney et al, 2008) and tsDCS (Berra et al, 2019).…”

“…Anodal tsDCS may represent a potentially self-administered NIBSS technique in those clinical conditions that are characterized by changes in spinal cord interneurons, and was found to inhibit nociceptive specific responses, such as the nociceptive withdrawal reflex (NWR; Cogiamanian et al, 2011) and the NWR temporal summation threshold (TST; Perrotta et al, 2016), which may contribute to the pathogenesis of pain in MS (Berra et al, 2019).…”