The Use of Botulinum Toxin A as an Adjunctive Therapy in the Management of Chronic Musculoskeletal Pain: A Systematic Review with Meta-Analysis

Abstract

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 −0.89; 95% CI −1.91; 0.12; p = 0.08). Caution should be used when interpreting such results, since the studies displayed very high heterogeneity (I = 94%, p < 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.

Multidimensional Effectiveness of Botulinum Toxin in Neuropathic Pain: A Systematic Review of Randomized Clinical Trials

“…Although BoNT has been suggested as an effective treatment to counter neuropathic pain [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ], evidence in the literature is mainly focused on the unidimensional evaluation of pain, with different systematic reviews assessing the Visual Analogue Scale (VAS) or Numerical Rating Scale (NRS). Conversely, given the psychosocial and functional burden of neuropathic pain, a multidimensional assessment of this condition is needed, in order to promote a patient-centered approach.…”

The Relationship between Pain and Spasticity and Tell-Tale Signs of Pain in Children with Cerebral Palsy

“…Secondly, for the relationship between changes in localized pain and spasticity level, we found no significant correlation between the two after BoNT-mediated pain reduction. We expected that changes in pain and spasticity levels were correlated [ 4 , 10 , 20 ] because it is generally assumed that pain and spasticity are closely interrelated [ 20 , 27 ] ( Table 1 ). Our findings suggest that pain reduction, and thus pain, is mediated by mechanisms other than inherent spasticity.…”

“…A focus on spasticity in pain management treatment in CCP using treatment with BoNT might explain why previous studies have been unable to identify a relationship between pain and spasticity [ 19 , 20 ]. If pain cannot be relieved by reducing spasticity via blocking nerve impulse relay, then pain in CCP might be caused by simple muscular overload or inhibition of the release of the neurotransmitters of pain [ 4 , 10 , 20 ]. This finding is significant because the primary intervention for musculoskeletal pain entails non-surgical treatments such as therapeutic exercise, weight loss, and patient education as first-line interventions [ 10 ].…”

“…Caregivers report that up to 67% of CCP are in pain [ 4 , 5 ], thus pain is a significant clinical problem [ 6 ]. The incidence increases with age and the severity of the disease [ 7 ], and it is often presumed in both research and clinical practice that there is a relationship between spasticity/muscle contractures/joint deformity and pain in both children and adults [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. However, the interrelationship is not fully understood, and other causalities not directly related to spasticity have been proposed such as musculoskeletal-derived pain, inhibition of the release of the neurotransmitters of pain mediate pain modulation, mediating an effect on central or peripheral sensitization instead of reducing spasticity by blocking nerve impulse relay [ 4 , 10 , 20 , 21 ].…”

“…The incidence increases with age and the severity of the disease [ 7 ], and it is often presumed in both research and clinical practice that there is a relationship between spasticity/muscle contractures/joint deformity and pain in both children and adults [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. However, the interrelationship is not fully understood, and other causalities not directly related to spasticity have been proposed such as musculoskeletal-derived pain, inhibition of the release of the neurotransmitters of pain mediate pain modulation, mediating an effect on central or peripheral sensitization instead of reducing spasticity by blocking nerve impulse relay [ 4 , 10 , 20 , 21 ]. AbobotulinumtoxinA/Dysport (BoNT) can be used to evaluate whether this interrelationship between spasticity and pain exists [ 4 , 20 , 21 ] because BoNT has a documented antispastic effect and has been utilized to modulate spasticity for 2 decades [ 22 , 23 ].…”