Abstract Background/Aims Exercise has shown a promising effect in reducing central sensitisation (CS), but it is unknown which exercise type is the most effective. This review aimed to rank and compare the effectiveness of different exercise interventions on CS in people with or without chronic musculoskeletal pain. This will help to identify the optimal exercise intervention to improve pain by reducing CS for subsequent use in clinical trials. Methods We searched MEDLINE, EMBASE, AMED, CINAHL, SPORTDiscus, CENTRAL, PEdro, SCOPUS, as well as references cited in the selected papers, and grey literature from inception to February 2022. We included randomized controlled trials (RCTs) that assessed the effect of exercise interventions on CS indices in humans. RCTs where a specific effect of exercise could not be determined were excluded. Pairwise and network meta-analyses (frequentist and Bayesian) were conducted using random effects models. Effect sizes were calculated using standardized mean difference (SMD). P-score as well as SUCRA score were used to rank the exercise interventions (from best to worst) in both frequentist and Bayesian approaches, respectively. Results The search returned 93,657 records, of which 143 RCTs (5,362 participants [4890 participants had musculoskeletal pain (122 studies), and 427 were pain free (21 studies)]) were eligible. Firstly, we performed the pairwise meta-analysis to examine the effect of all exercise interventions on all CS outcomes. It showed moderate improvement of CS outcomes (SMD - 0.77, 95% confidence interval (95%CI) -0.89 to -0.65, I2 = 87%, p < 0.01). After that, 80 RCTs were included in the network meta-analysis (NMA) using inactive controls as a common comparator. In terms of efficacy at improving indices of CS, all exercise interventions were more effective than control. Combined strengthening and stretching exercise exhibited the highest probability to be the optimal intervention reducing CS (P-score: 0.8896, SUCRA score: 0.8719, SMD= -2.02, 95%CI: -2.83: -1.20), followed by strengthening, stretching and aerobic combination (P-score: 0.8557, SUCRA score: 0.8517, SMD = -1.92, 95%CI: -2.90: -0.95), and stretching with aerobic exercise (P-score: 0.7794, SUCRA score: 0.7198, SMD = -1.70, 95%CI: -2.79: -0.62). However, differences between these three interventions’ effect sizes were small, and 95% CI were overlapping. Other interventions included, mind body exercise, aerobic plus strengthening exercise, strengthening exercise, stretching exercise, aerobic exercise. Conclusion Our meta-analysis suggested that various exercise interventions are effective in improving CS. Multicomponent exercise tends to be the most effective, but some exercise combinations might be better than others. Strengthening and stretching combination shows the greatest likelihood among other combinations of being the optimal exercise type. These findings might have utility informing future treatment recommendations for people with CS features. However, Further research should be considered to explore cost-effectiveness of different interventions. Disclosure A.A. Abd Elkhabir: None. D.F. McWilliams: Grants/research support; grant support from Pfizer and Eli Lilly. S. Smith: None. W. Chaplin: None. M. Salimian: None. V. Georgopoulos: None. A. Kouraki: None. D.A. Walsh: Consultancies; Since 2015 DAW has undertaken consultancy through the University of Nottingham to AbbVie Ltd, Pfizer Ltd, Eli Lilly and Company, Love Productions,, Reckitt Benckiser Health Limited and GSK (each non-personal, pecuniary). Honoraria; He has contributed to educational materials through the University of Nottingham, supported by Medscape Education, New York,, International Association for the Study of Pain, and Osteoarthritis Research Society International (OARSI), each of which received financial support from commercial and non-commercial entities, (each non-personal, pecuniary).. Member of speakers’ bureau; He has received speaker fees from the Irish Society for Rheumatology (personal pecuniary).. Grants/research support; He has been responsible for research funded by Pfizer, Eli Lilly, UCB Pharma (non-personal, pecuniary). Other; He receives salary from the University of Nottingham, who have received funding for that purpose from Sherwood Forest Hospitals NHS Foundation Trust,, Nottingham University Hospitals NHS Trust and UKRI/Versus Arthritis (personal, pecuniary).
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