A randomized phase I trial evaluating the effects of inhaled 50-50% N2O-O-2 on remifentanil-induced hyperalgesia and allodynia in human volunteers

作者：Wehrfritz A^*; Schaefer S; Troester A; Noel N; Bessiere B; Apiou Sbirlea G; Simonnet G; Schuettler J; Richebe P

来源：European Journal of Pain, 2016, 20(9): 1467-1477.

DOI：10.1002/ejp.870

BackgroundOpioids are known to relieve pain, and also aggravate pre-existing hyperalgesia. In animal studies, the N-methyl-d-aspartate-receptor antagonist nitrous oxide (N2O) was able to prevent hyperalgesia. The present study evaluated the effect of N2O on hyperalgesia after remifentanil infusion in healthy volunteers.
MethodsTwenty-one healthy volunteers were enrolled in this placebo-controlled cross-over study. Transcutaneous electrical stimulation at high current densities induced spontaneous acute pain and stable areas of hyperalgesia. Each volunteer underwent the following four sessions: (1) 50-50% N-2-O-2 and i.v. saline; (2) 50-50% N-2-O-2 and i.v. remifentanil 0.1g/kg/min; (3) 50-50% N2O-O-2 and i.v. saline; (4) 50-50% N2O-O-2 and i.v. remifentanil 0.1g/kg/min. Inhaled gas mixtures lasted for 60min, i.v. drug administration for 30min. Visual analogue scale pain intensity, areas of pinprick hyperalgesia and touch-evoked allodynia were assessed repeatedly for 160min.
ResultsData of 19 volunteers were analysed. There were significant time and treatment effects regarding areas of hyperalgesia and allodynia (p<0.02). The area of hyperalgesia was significantly reduced in the N2O+remifentanil session compared to the remifentanil session (35.8822.37 vs. 43.5518.48cm(2), p=0.004). The area of allodynia was significantly reduced in the N2O+remifentanil session compared to the remifentanil session (29.95 +/- 16.15 vs. 34.80 +/- 15.35cm(2), p=0.008). The pain intensity was significantly reduced in the N2O+remifentanil session compared to the remifentanil session (37.96 +/- 12.78 vs. 42.15 +/- 13.34mm, p<0.0001).
ConclusionsNitrous oxide significantly reduced hyperalgesia, allodynia and pain intensity aggravated after remifentanil administration in a human volunteer model.
What does this study add?This study brings the evidence that N2O reduces the remifentanil aggravated secondary hyperalgesia in human volunteers exposed to a well-known model of electrical pain. N2O was able to oppose the hyperalgesia, the allodynia and the pain intensity consecutive to remifentanil use in this specific pain model.

• 出版日期2016-10