Exploring the relationship between trauma- and stressor-related disorders and top-down central sensitization: A systematic review and meta-analysis

Introduction Top-down central sensitization (TDCS), a condition in which the central nervous system amplifies and prolongs responses to peripheral stimuli, is associated with reduced quality of life, decreased work participation, increased healthcare utilization, and rising healthcare costs. This systematic review examined the association between trauma- and stressor-related disorders (TSRDs) and TDCS, and explored potential modifiers including TSRD type, adverse childhood experiences, and sex. Methods PubMed, Embase, PsycINFO, CINAHL, PROSPERO, ClinicalTrials.gov, and OpenGrey were searched (up to July 23, 2025), without language restrictions. Eligible studies included individuals with TSRDs and TDCS from cross-sectional, case-control, or cohort designs. Two reviewers independently performed study selection, risk of bias assessment (Newcastle-Ottawa Scale), data extraction, and applied GRADE to assess evidence quality. Random-effect meta-analyses were performed. Sensitivity analyses of low-risk-of-bias studies examined the robustness of primary outcomes. Results Forty-one studies were included (pooled N = 133,081). A strong positive association was found between TSRDs and TDCS (OR = 3.87, 95% CI: 3.12–4.80; I2 = 87.5%). TSRD type significantly moderated this association (p ' 0.01), but sex did not (p = 0.34). No studies evaluated adverse childhood experiences as moderators. Sensitivity analyses confirmed robustness (OR = 2.90, 95% CI: 2.45–3.44; I2 = 23%), and GRADE rated the evidence as moderate. Conclusion Patients with trauma- and stressor-related disorders have a substantially greater risk of developing top-down central sensitization. The type of disorder may affect the strength of this relationship. Future longitudinal and interventional studies should determine whether treating TSRDs alters the course of TDCS.