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. 2025 Oct 23:pnaf146.
doi: 10.1093/pm/pnaf146. Online ahead of print.

Dynamic Perioperative Changes in Baroreflex Sensitivity Predict Postoperative Pain

Heberto Suarez-Roca  1 , Negmeldeen Mamoun  2 , Andrey V Bortsov  1 , Joseph P Mathew  2
Affiliations

Dynamic Perioperative Changes in Baroreflex Sensitivity Predict Postoperative Pain

Heberto Suarez-Roca et al. Pain Med. .

Abstract

Objective: Although higher baroreflex sensitivity (BRS) is typically associated with reduced pain sensitivity, we previously reported that elevated preoperative BRS predicted greater postoperative pain after cardiothoracic surgery, a finding that challenges existing experimental evidence. This exploratory secondary analysis tested whether perioperative changes in BRS (ΔBRS) better predict postoperative pain severity.

Design: Exploratory secondary analysis of a prospective observational cohort.

Subjects: Seventy-two adults undergoing elective minimally invasive cardiothoracic surgery.

Methods: Spontaneous cardiovagal BRS was measured preoperatively (pain-free baseline) and on postoperative days (POD) 1 and 2 (during ongoing pain). Pain severity was assessed using the PEG scale. Inflammatory biomarkers (C-reactive protein, cytokines, albumin) were also measured. Multivariable regression models evaluated associations between BRS metrics and pain, adjusting for demographic, surgical, analgesic, and psychological covariates.

Results: Higher preoperative BRS was associated with greater postoperative BRS decline (ΔBRS) by POD2 (R2 = 0.12, p = 0.008) and with more severe pain on POD2 (R2 = 0.15, p = 0.003). ΔBRS was independently and inversely associated with pain severity (R2 = 0.09, p = 0.025) even after covariate adjustment. Although inflammatory markers increased postoperatively, they did not mediate these associations.

Conclusions: Steep perioperative BRS declines, particularly among individuals with initially high values, may reflect autonomic destabilization and reduced baroreflex-mediated inhibition of nociception. These findings identify ΔBRS as a dynamic and mechanistically informative predictor of postoperative pain. Perioperative BRS monitoring could support individualized risk stratification and guide interventions aimed at stabilizing autonomic function to improve recovery outcomes.

Keywords: Postoperative pain; autonomic nervous system; baroreflex sensitivity; cardiothoracic surgery; inflammatory markers.

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