Studies conducted in various animal models of joint pain showed an anti-nociceptive effect of intra-articular botulinum toxin type A (BoNT-A). Randomized controlled trials (RCTs) in humans suggest a potential effect but results are disparate.

To assess the efficacy and safety of intra-articular BoNT-A for the treatment of joint pain.

We conducted a systematic review of RCTs comparing the effects of intra-articular BoNT-A to other interventions on pain and activity limitations in the short (<3 months), intermediate (3–6 months) and long term (> 6 months), and their adverse effects, in people with joint pain. We performed a meta-analysis when appropriate. MEDLINE, EMBASE, ClinicalTrials.gov, CINHAL and ICTRP databases were searched from inception to July 9, 2023. Two independent reviewers selected eligible studies and extracted data in a standardized manner. The results of quantitative synthesis were expressed as the standardized mean difference (SMD) (95 % confidence interval).

We included 14 RCTs: 437 participants received an intra-articular injection of BoNT-A and 551 received another intervention. Overall, 7 RCTs (549 participants) compared intra-articular BoNT-A with an intra-articular treatment in the knee: short-, intermediate-, and long-term SMD were -0.35 (-0.82 to 0.12), -0.27 (-0.61 to 0.08), and -0.43 (-1.12 to 0.26) for pain and -0.44 (-0.96 to 0.07), -0.24 (-0.63 to 0.15) and -0.42 (-1.26 to 0.42) for activity limitations, respectively. Two RCTs (68 participants) in the shoulder and 1 RCT (60 participants) in the base-of-thumb showed reduced pain in the short term. Minor adverse events were not rare, but no serious adverse events related to intra-articular BoNT-A were reported.

Intra-articular BoNT-A may reduce joint pain in the short term for small and medium-sized joints (ie, base-of-thumb and shoulder), but not for large joints (ie, knee).

PROSPERO: CRD42021290157 (Date of first submission: 8 November 2021; Date of registration: 8 December 2021).