A randomized phase I trial evaluating the effects of inhaled 50-50% N2 O-O2 on remifentanil-induced hyperalgesia and allodynia in human volunteers

Wehrfritz A, Schäfer S, Tröster A, Noel N, Bessiere B, Apiou-Sbirlea G, Simonnet G, Schüttler J, Richebe P (2016)


Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 20

Pages Range: 1467-77

Journal Issue: 9

DOI: 10.1002/ejp.870

Abstract

Opioids are known to relieve pain, and also aggravate pre-existing hyperalgesia. In animal studies, the N-methyl-d-aspartate-receptor antagonist nitrous oxide (N2 O) was able to prevent hyperalgesia. The present study evaluated the effect of N2 O on hyperalgesia after remifentanil infusion in healthy volunteers.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 ?g/kg/min; (3) 50-50% N2 O-O2 and i.v. saline; (4) 50-50% N2 O-O2 and i.v. remifentanil 0.1 ?g/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.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 N2 O + remifentanil session compared to the remifentanil session (35.88 ± 22.37 vs. 43.55 ± 18.48 cm(2) , p = 0.004). The area of allodynia was significantly reduced in the N2 O + remifentanil session compared to the remifentanil session (29.95 ± 16.15 vs. 34.80 ± 15.35 cm(2) , p = 0.008). The pain intensity was significantly reduced in the N2 O + remifentanil session compared to the remifentanil session (37.96 ± 12.78 vs. 42.15 ± 13.34 mm, p < 0.0001).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 N2 O reduces the remifentanil aggravated secondary hyperalgesia in human volunteers exposed to a well-known model of electrical pain. N2 O was able to oppose the hyperalgesia, the allodynia and the pain intensity consecutive to remifentanil use in this specific pain model.

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APA:

Wehrfritz, A., Schäfer, S., Tröster, A., Noel, N., Bessiere, B., Apiou-Sbirlea, G.,... Richebe, P. (2016). A randomized phase I trial evaluating the effects of inhaled 50-50% N2 O-O2 on remifentanil-induced hyperalgesia and allodynia in human volunteers. European Journal of Pain, 20(9), 1467-77. https://dx.doi.org/10.1002/ejp.870

MLA:

Wehrfritz, A., et al. "A randomized phase I trial evaluating the effects of inhaled 50-50% N2 O-O2 on remifentanil-induced hyperalgesia and allodynia in human volunteers." European Journal of Pain 20.9 (2016): 1467-77.

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