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

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.

Cutaneous silent period in hand muscles is lengthened by tramadol: Evidence for monoaminergic modulation?

The purpose of this study was to shed light on the neurochemical modulatory mechanisms of the noxious spinal inhibitory cutaneous silent period (CSP). We study the effects of 100mg of oral tramadol in 11 healthy volunteers. Tramadol has low affinity for opioid receptors and has the ability to inhibit serotonin and noradrenaline reuptake. We elicited CSPs in the first dorsal interosseus muscle and noxious withdrawal flexor reflexes (NWR) in the right biceps femoris muscle before, 30 min and each hour up to the 6th after tramadol. Subjective pain sensation was checked on an 11-point numerical scale. Tramadol increased duration of CSP, and reduced the NWR area under the curve maximally 2h after tramadol and paralleled the reduction of subjective pain perception. We suggest that the monoaminergic action of tramadol reinforces the activity of spinal inhibitory interneurons on α-motoneurons for the hand muscles.