Childhood adversity and provoked cytokine expression as overlapping influences on pain-related signalling.

Bedwell, Gillian

Childhood adversity and provoked cytokine expression as overlapping influences on pain-related signalling.

Thesis / Dissertation

2026

Publisher

University of Cape Town

Department

Department of Anaesthesia and Perioperative Medicine

Faculty

Faculty of Health Sciences

Abstract

Understanding the physiology of specific clinical features of persistent pain, such as SH, is crucial for developing effective treatments. This systematic review and meta-analysis investigated the effects of pharmacological manipulations on the magnitude (primary outcome) and surface area (secondary outcome) of experimentally induced SH. Following Cochrane Collaboration guidelines and a published and registered protocol, we conducted an electronic search on 07 February 2024. After screening articles in duplicate, we included 117 articles, consisting of 222 datasets. Risk of bias assessments identified potential flaws in methodological quality. Datasets were pooled by the mechanism of action of the manipulation and by outcome. Effect sizes were estimated using standardized mean difference (SMD). Most datasets (207 of 222) had an unclear risk of performance and detection bias for inadequate reporting of blinding procedures. Thirteen different methods were used to induce, and 23 different manipulation classes were used to manipulate SH. The pooled SMDs [95%CI] suggested that alpha-2-delta subunit of voltage-gated calcium channel ligands reduced both the magnitude (-0.24 [-0.39; -0.08]) and surface area (-0.38 [0.59; -0.18]) of SH, and that both NMDA receptor antagonists (-0.36 [-0.55; -0.17]) and voltage-gated sodium channel blockers (-1.02 [-1.63; -0.42]) reduced only the surface area of SH. These results suggest a need to understand and compare the physiological underpinnings of the magnitude and surface area of SH, and to clarify the relative importance of magnitude vs anatomical spread (i.e. surface area) of SH to people living with pain.