Intravenous adenosine alleviates neuropathic pain: a double blind placebo controlled crossover trial using an enriched enrolment design.
Adenosine analogs produce analgesic actions in nociceptive paradigms and alleviate manifestations of neuropathic pain in nerve injury models in rodents. In humans, previous work indicates an analgesic effect for adenosine administered intravenously in postoperative and neuropathic pain. In this double blind placebo controlled crossover trial, we used an enriched enrolment design to determine the effects of intravenous adenosine (50 microg/kg/min over 60min) on neuropathic pain. In Phase 1 of the trial, adenosine was administered in an open label manner, while in Phase 2 adenosine was administered in a double blind placebo controlled manner to 23 adenosine responders who had experienced a 30% or greater response in the open trial. Outcome measures included the McGill pain questionnaire (MPQ), which generates a pain rating index (PRI), and contains a visual analog scale (VAS) of pain intensity, the neuropathy pain scale (NPS), and a VAS for pain relief. Subjects also graded the degree of allodynia and hyperalgesia using a VAS. Adenosine led to a significant reduction in spontaneous pain according to the MPQ-PRI, the MPQ-VAS and the VAS for pain relief. The NPS showed a pattern similar to the MPQ-PRI, with statistically significant reductions in scales 1 (intensity), 3 (hot), 6 (sensitive), 7 (itchy) and 9 (unpleasant). Adenosine also led to a significant reduction in pinprick hyperalgesia, but not in allodynia. Three patients from Phase 1 of the trial experienced long term resolution of their pain following intravenous adenosine (5,16,25 months). The results of this study support previous reports that indicate intravenous adenosine alleviates neuropathic pain and hyperalgesia.
Lynch
Mary Elizabeth
ME
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. mary.lynch@dal.ca
Clark
Alexander John
AJ
Sawynok
Jana
J
D000241:Adenosine / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D007262:Infusions, Intravenous / Q000379:methods; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010919:Placebos; D012677:Sensation; D012684:Sensory Thresholds / Q000187:drug effects; D013995:Time; D013997:Time Factors; D016896:Treatment Outcome
D000700:Analgesics; D010919:Placebos; D000241:Adenosine