Randomised double-blind active-placebo-controlled crossover trial of intravenous fentanyl in neuropathic pain

Background The effectiveness of opioid analgesics in noncancer neuropathic pain is unpredictable and can be disappointing. It is not clear whether opioids, when effective, relieve pain by decreasing pain intensity or pain unpleasantness or by their sedative effect. The aim of this prospective randomised double-blind placebo-controlled crossover trial was to assess relief of pain intensity and pain unpleasantness with intravenous infusions of fentanyl. Methods We compared the analgesic effect of intravenous dose titration of fentanyl with diazepam (active placebo) or saline (inert placebo) in 53 patients with different types of neuropathic pain. Patients were randomly assigned two consecutive infusions: fentanyl plus diazepam (27 patients) or fentanyl plus saline (26 patients). Study medication was infused at a constant rate for a maximum of 5 h. Pain, sedation, and sideeffects were assessed from the start of infusion for 8 h. The primary outcome measure was maximum relief of pain intensity. Findings One patient in the fentanyl/diazepam group and two in the fentanyl/saline group were withdrawn. Maximum relief of pain intensity was better with fentanyl than with diazepam (66% [95% Cl 53–80] vs 23% [12–35]) or with saline (50% [36–63] vs 12% [4–20]). The beneficial effect of fentanyl was independent of the type of neuropathic pain and the degree of sedation. Fentanyl therapy produced equal relief of pain intensity and pain unpleasantness, whereas diazepam and saline did not reduce either pain index. Patients reported significantly more side-effects while receiving fentanyl than during diazepam or saline infusion (p<0·0001), but none of the side-effects was severe. Interpretation Fentanyl may relieve non-cancer neuropathic pain by its intrinsic analgesic effect. The clinical characteristics of neuropathic pain do not predict response to opioids.