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 RIII 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 RIII reflex threshold increased and RIII 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 RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS.
Conte
Antonella
A
Department of Neurological Sciences, University of Rome "Sapienza", Viale dell'Università 30, 00185 Rome, Italy.
Bettolo
Chiara Marini
CM
Onesti
Emanuela
E
Frasca
Vittorio
V
Iacovelli
Elisa
E
Gilio
Francesca
F
Giacomelli
Elena
E
Gabriele
Maria
M
Aragona
Massimiliano
M
Tomassini
Valentina
V
Pantano
Patrizia
P
Pozzilli
Carlo
C
Inghilleri
Maurizio
M
D000284:Administration, Oral; D000328:Adult; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects; D002186:Cannabinoids / Q000008:administration & dosage* / Q000009:adverse effects; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010919:Placebos; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D000700:Analgesics; D002186:Cannabinoids; D010919:Placebos; D013759:Dronabinol