{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:03:16Z","timestamp":1783702996660,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Several studies have investigated the effect of botulinum toxin A (BoNT-A) for managing chronic musculoskeletal pain, bringing contrasting results to the forefront. Thus far, however, there has been no synthesis of evidence on the effect of BoNT-A as an adjunctive treatment within a multimodal approach. Hence, Medline via PubMed, EMBASE, and the Cochrane Library-CENTRAL were searched until November 2020 for randomised controlled trials (RCTs) that investigated the use of BoNT-A as an adjunctive therapy for chronic musculoskeletal pain. The risk of bias (RoB) and the overall quality of the studies were assessed through RoB 2.0 and the GRADE approach, respectively. Meta-analysis was conducted to analyse the pooled results of the six included RCTs. Four were at a low RoB, while two were at a high RoB. The meta-analysis showed that BoNT-A as an adjunctive therapy did not significantly decrease pain compared to the sole use of traditional treatment (SDM \u22120.89; 95% CI \u22121.91; 0.12; p = 0.08). Caution should be used when interpreting such results, since the studies displayed very high heterogeneity (I = 94%, p &lt; 0.001). The overall certainty of the evidence was very low. The data retrieved from this systematic review do not support the use of BoNT-A as an adjunctive therapy in treating chronic musculoskeletal pain.<\/jats:p>","DOI":"10.3390\/toxins13090640","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:48:01Z","timestamp":1631483281000},"page":"640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Use of Botulinum Toxin A as an Adjunctive Therapy in the Management of Chronic Musculoskeletal Pain: A Systematic Review with Meta-Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-1951","authenticated-orcid":false,"given":"Simone","family":"Battista","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Buzzatti","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, Human Physiology and Anatomy, Experimental Anatomy Research Group, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium"},{"name":"School of Allied Health, Anglia Ruskin University (ARU), Cambridge CB1 1PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0877-4807","authenticated-orcid":false,"given":"Marialuisa","family":"Gandolfi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"},{"name":"UOC Neurorehabilitation, AOUI Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4385-1203","authenticated-orcid":false,"given":"Cinzia","family":"Finocchi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-3200","authenticated-orcid":false,"given":"Luca","family":"Falsiroli Maistrello","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132 Genova, Italy"},{"name":"Department of Physical Medicine and Rehabilitation, AULSS9 Scaligera, G. Fracastoro Hospital, San Bonifacio, 37074 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1480-4061","authenticated-orcid":false,"given":"Antonello","family":"Viceconti","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0079-0714","authenticated-orcid":false,"given":"Benedetto","family":"Giardulli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8643-7200","authenticated-orcid":false,"given":"Marco","family":"Testa","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1136\/annrheumdis-2013-204680","article-title":"The global burden of other musculoskeletal disorders: Estimates from the Global Burden of Disease 2010 study","volume":"73","author":"Smith","year":"2014","journal-title":"Ann. 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