Naloxone provokes similar pain facilitation as observed after short-term infusion of remifentanil in humans.
In contrast to an expected preventive analgesic effect, clinical observations suggest that intraoperatively applied opioids can induce postoperative hyperalgesia. We tested the development of post-infusion hyperalgesia in a newly developed experimental model of electrically induced pain and secondary mechanical hyperalgesia. In a double-blind, placebo controlled, cross-over study, 13 subjects received either saline placebo, remifentanil (0.05 or 0.1 microg/kg/min) or naloxone (0.01 mg/kg). Remifentanil dose-dependently reduced pain and mechanical hyperalgesia during the infusion, but upon withdrawal, pain and hyperalgesia increased significantly above control level (p<0.01 and p<0.05, respectively). Naloxone infusion similarly resulted in increased pain (anti-analgesia) (p<0.001) and mechanical hyperalgesia (p<0.01). Increased pain ratings following withdrawal of remifentanil significantly correlated to anti-analgesia evoked by the mu-opioid antagonist naloxone (p<0.01) and was of similar magnitude, suggesting inhibition of endogenous opioids as an underlying mechanism. In contrast, hyperalgesia after remifentanil was more pronounced than hyperalgesia after naloxone administration and did not correlate to the observed anti-analgesic effects, suggesting the involvement of additional receptors systems other than the endorphin system.
Department of Anesthesiology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
Wolfgang
W
Koppert
Martin
M
Angst
Monika
M
Alsheimer
Reinhard
R
Sittl
Sven
S
Albrecht
Jürgen
J
Schüttler
Martin
M
Schmelz
D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects*; D018592:Cross-Over Studies; D020405:Dermis; D004558:Electric Stimulation; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced; D008297:Male; D009270:Naloxone / Q000009:adverse effects*; D009292:Narcotic Antagonists / Q000009:adverse effects*; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy; D010880:Piperidines / Q000009:adverse effects*; D017450:Receptors, Opioid, mu / Q000819:agonists; D000077208:Remifentanil; D012965:Sodium Chloride
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010880:Piperidines; D017450:Receptors, Opioid, mu; D009270:Naloxone; D012965:Sodium Chloride; D000077208:Remifentanil