A randomized phase I trial evaluating the effects of inhaled 50–50% N2O–O2 on remifentanil-induced hyperalgesia and allodynia in human volunteers

Abstract

Background

Opioids 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.

Methods

Twenty-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% N₂–O₂ and i.v. saline; (2) 50–50% N₂–O₂ and i.v. remifentanil 0.1 μg/kg/min; (3) 50–50% N₂O–O₂ and i.v. saline; (4) 50–50% N₂O–O₂ and i.v. remifentanil 0.1 μg/kg/min. Inhaled gas mixtures lasted for 60 min, i.v. drug administration for 30 min. Visual analogue scale pain intensity, areas of pinprick hyperalgesia and touch-evoked allodynia were assessed repeatedly for 160 min.

Results

Data 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 (35.88 ± 22.37 vs. 43.55 ± 18.48 cm², 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 ± 15.35 cm², 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 ± 13.34 mm, p < 0.0001).

Conclusions

Nitrous 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.

from European Journal of Pain http://ift.tt/1qkVjlN
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