Effects of buprenorphine on pain perception in healthy adults: a meta-narrative systematic review

The availability of knowledge about the effects of buprenorphine on pain perception in healthy adults could help investigators select experimental tests with evidence of responsiveness to buprenorphine in nondiseased states. The purpose of this meta-narrative systematic review is to summarize the effects of buprenorphine on pain perception in healthy adults. Comprehensive database searches were conducted from inception dates through July 16, 2024. Inclusion criteria included all study designs involving healthy adults receiving buprenorphine and tests of pain perception. Risk of bias was assessed using a tool developed for randomized controlled trials (RCTs). A meta-narrative approach was used due to high levels of clinical heterogeneity. A total of 10 RCTs were included, and healthy adults comprised the comparator groups in all trials. Three RCTs had a low risk of bias, 6 had some concerns, and 1 had a high risk of bias. Six RCTs used intravenous buprenorphine, 3 used transdermal, and 1 study used intravenous and sublingual buprenorphine. The effects of buprenorphine on pain perception are influenced by the route of administration, dose, and pain stimulus modality. Considerable differences exist in the effects of intravenous and transdermal buprenorphine, but only 1 study used sublingual buprenorphine, which limited comparison with the other drug formulations. Based on these findings, recommendations for clinical trials are proposed. These recommendations should be cautiously interpreted due to the clinical heterogeneity, but they provide a framework for advancing the use of experimental pain tests in trials of buprenorphine involving comparator groups of healthy adults.