The Effect of Opioid Blockade on Pain in Healthy Humans: A Systematic Review and Meta-Analysis
Year: 2021
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Background: Although several observations indicate that endogenous opioids regulate pain and support analgesia, pharmacological blockade of opioid activity does not consistently worsen pain in experiments.Insufficient elimination of opioid responses is one possible reason for the discrepancy between studies, but this has not been investigated.It is also unclear whether endogenous opioids selectively modulate pain under specific conditions.Objective: To establish the impact of complete opioid blockade on pain outcomes and clarify in which instances pain regulation is opioid dependent, we conducted a systematic review and meta-analysis of experimental pain studies in healthy humans.Methods: We searched Web of Science, Scopus, PubMed and EMBASE on October 7, 2020.Eligible studies were at least double-blind, randomized, and placebo-controlled, used physiological pain interventions, and administered a centrally active μ-opioid antagonist.Quality assessments of each study and funnel plots were used to evaluate risk of bias.To compare treatment effects on pain responses, we calculated Hedges' g for individual outcomes and used a three-level random effects meta-analysis to estimate the summary effect.This work was an independent project.Data collection was performed by the thesis author and the thesis presents preliminary results.Results: A total of 60 studies (n = 2011) were included in the analyses.Most studies measured pain intensity and used the antagonist drug naloxone and thermal pain stimulation.Overall, experimental pain responses were significantly higher with full μ-opioid blockade compared to conditions where participants received a pharmacologically inert substance (Hedges' g [95% CI] = 0.23 [0.10, 0.36]), but there was considerable heterogeneity present (I 2 = 77.2%).While pain intensity, tolerance and threshold worsened with opioid blockade, pain unpleasantness was not significantly altered.There were no substantial differences between brief and prolonged pain stimuli.Conclusion: Complete blockade of endogenous opioids appears to produce a small increase in pain sensitivity in experimental pain models in healthy humans.However, due to reporting bias in the literature, the size of this effect may be overstated.Further investigation is needed to assess the reasons for the observed variability.2 Methods .........
Author: Eira Nordeng Jensen
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3203381864