729: Descending Pain Modulation and Motor Responses in Pain: A Systematic Review and Meta-Analysis

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Electrophysiology, Assessment and Measurement of Pain/Nociception, Behavioral studies

Background and Aims: Descending pain modulation, commonly assessed using dynamic quantitative sensory testing (QST) paradigms such as conditioned pain modulation (CPM), temporal summation of pain (TSP), and offset analgesia (OA), reflects the balance between inhibitory and facilitatory processes in the central nervous system [1-4]. Dysregulation of these mechanisms is a hallmark of chronic pain [5-8]. Beyond pain perception, emerging evidence suggests a functional link between pain modulation and the motor system [9-11]. However, existing research has only focused on CPM effects at reflex-level outcomes in healthy individuals [11], with limited synthesis of other types of QST and voluntary motor responses. This systematic review and meta-analysis aimed to evaluate how descending pain modulation influences motor responses in individuals with clinical or experimentally induced pain.

Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines [12] and registered in PROSPERO (CRD42024527363). A comprehensive search was performed in Medline, Embase, Web of Science, and CINAHL from inception to July 2025. Two reviewers independently screened studies and extracted data. Eligible studies included human participants with clinical or experimentally induced pain and examined descending pain modulation using CPM, TSP, or OA in relation to motor responses (e.g., muscle activity or performance). Risk of bias was assessed using a modified Newcastle–Ottawa Scale [11,13]. Meta-analyses were conducted using random-effects models, calculating standardized mean change (Hedges’ g) to account for within-subject designs. Heterogeneity was assessed using I², and certainty of evidence was evaluated using the GRADE approach [14].

Results: The search identified 6,268 records, of which 18 studies (n = 416 participants) were included and 13 were eligible for meta-analysis. Most studies assessed conditioned pain modulation (CPM), with limited data on temporal summation of pain (TSP) and no studies on offset analgesia (OA). All included studies evaluated reflex-based motor outcomes.

Meta-analysis showed that CPM exerted a large inhibitory effect on nociceptive withdrawal/flexion reflex (NWR/NFR) amplitude (Hedges’ g = −1.16, 95% CI: −2.05 to −0.28) and a very large inhibitory effect on threshold-based outcomes (Hedges’ g = −1.80, 95% CI: −2.50 to −1.10). In contrast, CPM effects on the nociceptive blink reflex (nBR) were small and non-significant (Hedges’ g = −0.30). TSP demonstrated a large facilitatory effect on NWR/NFR threshold (Hedges’ g = 1.69, 95% CI: 0.36 to 3.03). Evidence certainty ranged from very low to moderate.

Conclusions: This systematic review and meta-analysis suggests that descending pain modulation is associated with motor system responses in individuals with pain conditions. Conditioned pain modulation (CPM) demonstrated inhibitory effects on spinal nociceptive reflexes, whereas temporal summation of pain (TSP) showed facilitatory effects, supporting the interaction between inhibitory and facilitatory pain mechanisms and motor output. However, evidence remains limited to reflex-based outcomes, with no studies investigating voluntary motor responses or offset analgesia (OA). Substantial heterogeneity and generally low-to-moderate certainty of evidence highlight the need for cautious interpretation. Notwithstanding, this review offers greater insight into how descending pain modulation exerts its influence at various hierarchical levels of the motor control pathway. Future research should examine voluntary motor outcomes and integrate multiple QST paradigms using standardized protocols to better understand how pain modulation influences motor function.

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Presenting Author: Xianhua Zeng
Submitting Author: Xianhua Zeng

Senior Author: Gwendolyne G.M. Scholten-Peeters

IASP 2026 Global Year theme of Neuropathic Pain: No

• Marco Griseri - Rehabilitation Research Laboratory 2rLab, Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Switzerland
• René Castien - Department of Human Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
• George Louis Burchell - Medical Library, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
• Marijtje Jongsma - Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands; Faculty of Psychology, University Gadjah Mada, Yogyakarta, Indonesia
• Jaap H van Dieën - Department of Human Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
• Jessica Van Oosterwijck - Spine, Head and Pain Research Unit, Department of Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Ghent University. Ghent, Belgium; Pain in Motion international research consortium, http://www.paininmotion.be/
• Gwendolyne G.M. Scholten-Peeters - Department of Human Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands