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.

The cholecystokinin antagonist proglumide enhances the analgesic effect of dihydrocodeine.

AIM: To investigate the potential pro-analgesic effect of the non-specific CCK antagonist proglumide on the analgesia produced by dihydrocodeine. METHOD: A double-blind, placebo-controlled crossover study of 30 adult subjects. RESULTS: Mean pain scores fell from a baseline of 8.12-7.89 during the placebo phase (N.S.) and to 6.82 during the proglumide phase (P < 0.05). Side effects were minor. CONCLUSION: The CCK antagonist proglumide enhances the analgesic effect of dihydrocodeine.

A randomised, double blind, placebo controlled crossover study of the cholecystokinin 2 antagonist L-365,260 as an adjunct to strong opioids in chronic human neuropathic pain.

The aim of this study was to establish if the cholecystokinin (CCK) 2 antagonist L-365,260 augments the analgesic effect of morphine in human subjects with chronic neuropathic pain. This is a randomised, double blind, placebo controlled study of 40 adult subjects taking morphine for neuropathic pain. Each received placebo, L-365,260 30 mg and L-365,260 120 mg in three divided doses daily separated by a washout period in random order. Pain, activity, sedation, sleep and side effects were recorded along with 12 lead ECGs, renal and liver function tests and full blood pictures. L-365,260 failed to augment the analgesic effect of morphine at any of the dose levels used. Side effects were minor. There were no changes in ECGs and biochemical indices were unaltered with its use. The CCK 2 antagonist L-365,260 does not augment the analgesic effect of morphine in subjects with chronic neuropathic pain. L-365,260 was well tolerated and side effects from its use were minor.

A phase 1 study of the cholecystokinin (CCK) B antagonist L-365,260 in human subjects taking morphine for intractable non-cancer pain.

To investigate the safety and tolerability of L-365,260 in human subjects taking morphine for intractable pain. An open label study of nine adult subjects. Two doses of L-365,260 were administered to all subjects separated by a 4 h interval (three received 10 mg, three 30 mg and three 60 mg). Haemodynamic and respiratory variables were recorded from immediately prior to first drug administration to T + 600 min. In addition, continuous electrocardiogram (ECG) monitoring and serial 12 lead ECGs were recorded along with pain and side effect measurements. No major side effects were observed. L-365,260 was well tolerated. No abnormalities in blood pressure, heart rate, respiratory rate or ECG measurements were recorded. Minor side effects were observed. L-365,260 can be safely administered at the doses investigated to human subjects receiving morphine for intractable pain.

Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report.

The objective of this case report is to emphasize the analgesic effect of antiepileptic drugs in those with neuropathic pain, confirm that fosphenytoin possesses these analgesic properties, and to highlight that intravenous administration of fosphenytoin for 24 hours can produce good quality pain relief that lasts for many weeks. A 37-year-old woman with a neuroma (caused by surgical intervention for an endometrial sarcoma) producing neuropathic pain unresponsive to opiates was successfully treated with intravenous infusion of 1,500 phenytoin equivalent units fosphenytoin for 24 hours. The pain relief after this and subsequent infusions persisted for between 3 and 14 weeks and was associated with a reduced opiate requirement and an increase in activities of daily living. Fosphenytoin infusion can give good quality pain relief in the patient with neuropathic pain.

Intravenous phentolamine mesylate alleviates the pain of pancreatic carcinoma.

This case report describes the successful alleviation of the pain of pancreatic carcinoma with intravenous phentolamine mesylate. A 2 day infusion gave relief for 26 days on the first occasion and for 12 weeks after the second infusion. The possible mode of action is discussed.