Altered Pain Perception and Nociceptive Thresholds in Major Depression and Anxiety Disorders: A Meta-Analysis

Simona Scaini; Simon Davies; Stefano De Francesco; Alessio Pelucchi; Sofia Rubino; Marco Battaglia

doi:10.1016/j.neubiorev.2025.106014

Altered Pain Perception and Nociceptive Thresholds in Major Depression and Anxiety Disorders: A Meta-Analysis

Neurosci Biobehav Rev. 2025 Jan 17:106014. doi: 10.1016/j.neubiorev.2025.106014. Online ahead of print.

Authors

Simona Scaini¹, Simon Davies², Stefano De Francesco³, Alessio Pelucchi³, Sofia Rubino³, Marco Battaglia⁴

Affiliations

¹ Child and Youth Lab, Sigmund Freud University, Milan, Italy; Child and Adolescent Unit, Italian Psychotherapy Clinics, Milan, Italy. Electronic address: s.scaini@milano-sfu.it.
² Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, ON, Canada.
³ Child and Youth Lab, Sigmund Freud University, Milan, Italy.
⁴ Department of Psychiatry, University of Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada; Cundill Centre for Child and Youth Depression, Toronto, ON, Canada.

PMID: 39828235
DOI: 10.1016/j.neubiorev.2025.106014

Abstract

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.

Keywords: Anxiety Disorders; Major Depressive Disorder; Meta-analysis; Pain threshold; nociception.

Publication types

Review