Does a single intravenous injection of the 5HT3 receptor antagonist ondansetron have an analgesic effect in neuropathic pain? A double-blinded, placebo-controlled cross-over study.

UNLABELLED Neurokinin-1-expressing neurones in lamina I to III of the spinal cord are intimately involved in the regulation of ascending and spino-bulbal pathways that regulate excitatory transmission. In experimental animals, ablation of these neurones reduces the responses to a variety of nociceptive stimuli. Furthermore, in animals, spinal application of the selective 5HT3 receptor antagonist ondansetron mimics these effects, indicating that 5HT3 receptors play a pronociceptive role and mediate descending excitatory controls that allow spinal neurones to fully code peripheral stimuli. In this study, we examined the potential analgesic effect of a single IV injection of ondansetron in humans with chronic neuropathic pain. Each consenting subject received a single IV injection of 8 mg ondansetron and placebo in varying order at least 1 wk apart with pain scores being recorded for the 48 h preceding and after each injection. Pain scores were significantly reduced 2 h after ondansetron injection (but at no other time point). This suggests that ondansetron can have an analgesic effect in neuropathic pain. Side effects were minor and infrequent. IMPLICATIONS The selective 5HT3 receptor antagonist ondansetron, currently used as an antiemetic, may also have analgesic properties. Side effects with a single IV injection are infrequent and usually mild.