Altered pain perception and nociceptive thresholds in major depression and anxiety disorders: A meta-analysis

Psychiatric conditions can affect the experience of pain. Several reports indicate that Major Depressive Disorder (MDD) is associated with an increased pain threshold, while Anxiety Disorders (ADs) may amplify the perception of pain. However, available data on the nociceptive threshold in these psychiatric conditions are controversial. This meta-analysis examines: 1) the nociceptive threshold among people diagnosed with MDD or ADs compared to healthy controls, and 2) the available evidence that pharmacological treatments affect these relationships. Electronic searches were conducted in PubMed and PsycINFO between June 2022 and December 2024. A total of 25 studies were included. "Pain threshold" measurement was considered as a direct comparison between subjects affected by MDD or ADs (both medicated and unmedicated) and healthy control subjects. For each study, the effect size (ES) was calculated, with a positive ES indicating a lower pain threshold. The heterogeneity of the specific set of effect sizes and the effects of selected moderators were tested using the I² index and the Q statistic. Results indicated that patients with Major Depressive Disorder (MDD) had a higher pain threshold (ES: −0.60), while those with Anxiety Disorders (ADs) had a lower pain threshold (ES: −0.34) compared to healthy controls. These findings were confirmed when analyses were limited to studies of unmedicated patients. Exploratory analyses restricted to studies containing medicated MDD patients were inconclusive, and for medicated ADs patients, analyses were not possible due to insufficient data. These meta-analytic data support higher pain threshold associated with MDD, and lower pain threshold associated with ADs.