Sleep, inflammation, and pain in musculoskeletal rehabilitation: a structured integrative review of neurobiological mechanisms and non-pharmacological pain management strategies

22/10/2026

AI Summary

Sleep disturbance, inflammation and persistent pain interact bidirectionally, reinforcing each other and undermining musculoskeletal rehabilitation.
Sleep restriction modulates inflammatory mediators (IL-6, TNF-α, CRP), with variable responses across populations and experimental protocols.
Exercise, manual therapy, NMES, low level laser and sleep-focused behavioural interventions show mechanistic plausibility; include sleep assessment in multimodal care and require confirmatory trials.

Pain Manag. 2026 Oct 20:1-13. doi: 10.1080/17581869.2026.2748285. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep disturbance, inflammation, and persistent pain may reinforce one another, compromising musculoskeletal rehabilitation.

PURPOSE: To synthesize evidence on mechanisms linking sleep, inflammation, and pain and identify relevant non-pharmacological interventions.

METHODS: This structured integrative review examined peer-reviewed studies published from January 2010 to December 2025, identified through PubMed, Scopus, PEDro, and SciELO. Reporting and synthesis were guided by SANRA and EQUATOR recommendations.

RESULTS: Fifty-seven studies were included: 24 experimental or observational studies, 17 systematic reviews or meta-analyses, and 16 narrative or integrative reviews. Sleep restriction was associated with changes in interleukin-6, tumor necrosis factor-α, and C-reactive protein, with responses varying across populations and protocols. Prostaglandins and bradykinin may promote nociceptive sensitization, while disrupted sleep may impair descending pain inhibition. Exercise, manual therapy, neuromuscular electrical stimulation, low-level laser therapy, and sleep-focused behavioral interventions showed mechanistic plausibility, although confirmatory trials remain limited.

CONCLUSION: Sleep assessment and sleep-focused interventions should be considered within multimodal musculoskeletal pain management, while further controlled research clarifies clinical effectiveness.

PMID:42902543 | DOI:10.1080/17581869.2026.2748285

Document this CPD