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

Abstract

Sleep disturbance, inflammation, and persistent pain may reinforce one another, compromising musculoskeletal rehabilitation. To synthesize evidence on mechanisms linking sleep, inflammation, and pain and identify relevant non-pharmacological interventions. 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. 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-&#x3b1;, 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. Sleep assessment and sleep-focused interventions should be considered within multimodal musculoskeletal pain management, while further controlled research clarifies clinical effectiveness. <b>Why was this study done?</b> Sleep problems, inflammation, and pain are closely linked. When people do not sleep well, the body may make more molecules that cause inflammation, which can lower the ability to cope with pain and make recovery harder. This can turn into a cycle that keeps pain going. We looked at recent research to understand how these three things affect each other and what health professionals including pain doctors and physiotherapists can do about it.<b>What did we find?</b> Poor sleep is linked with body changes that may make pain feel worse. Treatments that do not rely on medicines such as aerobic exercise, strength training, hands-on (manual) therapy, and sleep education may help lower pain by improving inflammation, calming the nervous system, building confidence in movement, and improving sleep. Stronger proof from high-quality trials is still needed.<b>What does this mean for patients?</b> Health professionals should ask patients about their sleep as a routine part of care. Adding sleep-focused strategies to musculoskeletal pain care may help some patients, but this still needs to be confirmed by high-quality clinical trials.