Experiment-Induced Nociception in Humans with Substance Use Disorders: A Review of Psychophysical Studies.

Abstract

Pain perception in individuals with substance use disorders (SUDs) is shaped by neuroadaptive changes in both peripheral and central nociceptive pathways. Accurate assessment of pain sensitivity in this population is essential for effective clinical management but remains challenging due to overlapping effects of drug use, tolerance, and withdrawal. This review synthesizes findings on pain sensitivity in individuals with SUDs, focusing on experimentally induced nociception-specifically thresholds, tolerance, and perceived intensity of pain. A systematic narrative review. Clinical studies that involve patients with opioid, alcohol, and stimulant use disorders and compare their pain responses to those of healthy controls. The protocol for this review was registered on Open Science Framework (ID# XYPE6). A comprehensive PubMed search identified studies assessing nociception in SUD populations, focusing on pain threshold, tolerance, and intensity. Of 348 publications, 14 studies were included. Thermal stimuli (cold and heat) were used most frequently, followed by pressure, electrical, and chemical modalities. Findings indicate changes in pain thresholds and increased pain sensitivity in association with SUDs, with evidence of dysesthesia notably in patients with alcohol, stimulant, and tobacco use disorders, as well as in chronic pain patients receiving opioids. This review is limited by the scarcity of clinical psychophysical pain studies in SUD populations, since most existing research is based on animal models. Additionally, heterogeneous testing protocols across studies constrain comprehensive synthesis. Changes in experimentally induced nociception among individuals with SUDs are measurable and extend beyond preclinical findings. Psychophysical assessments during specific withdrawal stages can reliably quantify nociception in this population. Further research using standardized methodologies is needed to bridge preclinical and clinical evidence and thus enhance pain management strategies for individuals with SUDs.