What is the role of botulinum toxin (BTX) injection for the treatment of osteoarticular pain?

Updated: Jun 19, 2018
  • Author: Anthony H Wheeler, MD; Chief Editor: Meda Raghavendra (Raghu), MD  more...
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The rationale for the use of BTX injections into painful joints followed research findings that implicated intra-articular injections of substance P and calcitonin gene-related peptide (CGRP) as causative of joint pain and inflammation. BTX was found to produce significant pain relief when injected into painful joints due to either inflammatory or noninflammatory disorders. This rationale presumes that the neurotoxin is capable of binding to nocicepter C-fibers, undergoing endocytosis, and blocking the vesicular release of substance P, CGRP, and glutamate, which are all pain mediators capable of producing neural transmission of noxious stimuli with subsequent nocicepter sensitization.

Mahowald et al reviewed their clinical experience with 11 patients (15 joints) who were treated for refractory joint pain with intra-articular injections of BTX-A over 12 months. [79] None were considered to be surgical candidates, and all had failed multiple oral and intra-articular medication treatments. Fifteen joints were managed by intra-articular injections of BTX-A. Six lower extremity joints (3 knees, 3 ankles) received 25-50 U, and 9 shoulders were treated with 50-100 U. Maximum relief of pain, maximum improvement in function, and the time to perform sit-to-stand 10 times (the timed stands test [TST]) were used as outcome measures for the lower extremity joints.

Five patients had osteoarthritis (OA), 5 had rheumatoid arthritis (RA), and 1 had psoriatic arthritis. A clinically and statistically significant improvement was noted after IA-BTX-A injections. The mean maximum decrease in lower extremity joint pain was 55%, and a 36% improvement in the TST was noted at 4-10 weeks after injection. A 71 % mean maximum reduction in shoulder pain severity was noted. Active range of motion increased 67% in flexion and 42% in abduction. No significant adverse effects related to BTX-A were noted. Duration of pain relief ranged from 3-12 months. Although this study was small and uncontrolled, the results suggest that IA-BTX-A injections are an effective and safe treatment for chronic joint pain.

Singh et al performed a randomized, double-blind, randomized controlled trial to determine the safety and efficacy of intra-articular BTX-A injections in 43 patients with chronic refractory, moderate-to-severe shoulder joint pain presumed to be due to arthritis. [80] Patients were randomized to receive either 100 U of BTX-A with lidocaine or saline and lidocaine. Primary outcomes were reduced pain severity on VAS at 1 month (0-10 cm). Secondary outcomes were improvements as measured by the Shoulder Pain and Disability Index (SPADI) disability subscale, quality of life on short-form (SF)-36 subscales, percent of patients who achieved at least a 30% decrease or a 2-point reduction in VAS pain (clinically meaningful pain relief), and safety.

Both BTX-A (n = 21) and placebo (n = 22) groups were comparable at baseline. At one month postinjection, pain reduction by VAS, SF-36 subscale scores, and the SPADI disability subscale improvement were significantly greater in the BTX-A group than in the placebo group. Clinically meaningful pain relief occurred in 61% of the BTX-A treatment group versus 36% of placebo patients (P = 0.22). The total number of adverse events was similar, which included 50 events in the BTX-A group versus 46 events in the placebo group. Therefore, a single injection of BTX-A produced statistically significant and clinically meaningful pain relief and improvement in quality of life in patients with chronic refractory moderate/severe shoulder arthritis pain at 1 month. These data provided evidence to support the need for a larger multicenter, randomized trial.

The effect of BTX-A on pain and functional impairment caused by refractory plantar fasciitis was investigated using a randomized, double-blind, placebo-controlled study of 27 patients (43 feet) with plantar fasciitis. [81] In patients with comparable bilateral severity, BTX-A was injected in one foot and saline in the other. BTX-A at 70 U was divided into 2 sites per foot. Placebo was the same volume of normal saline. Main outcome measures included pain VAS, Maryland Foot Score, pain relief VAS, and pressure algometry response. Patients were assessed at baseline, 3 weeks, and 8 weeks. Compared with placebo injections, the BTX-A group improved in all measures.

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