Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis

Although clinical Studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients' electrophysiological responses to noxious Stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control.In a randomized, double-blind, placebo-controlled, cross-over study we investigated cannabinoid-induced changes in Rill reflex variables (threshold, latency and area) in a group of 18 patients with secondary Progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H-reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the Study. After patients used a commercial delta-9-tetrahydrocannabinol (THC) and cannabidiol Mixture as an oromucosal spray the Rill reflex threshold increased and Rill reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy.In Conclusion, the cannabinoid-induced changes in the Rill reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS, (C) 2008 Published by Elsevier Ltd. on behalf of European Federation of Chapters of the International Association for the Study of Pain.