Botulinum Neurotoxin for the Treatment of Neuropathic Pain

Botulinum neurotoxins (BoNTs) are potent inhibitors of synaptic vesicle fusion and transmitter release. The natural target of BoNTs is the peripheral neuromuscular junction (NMJ) where, by blocking the release of acetylcholine (ACh), they functionally denervate muscles and alter muscle tone. This leads them to be an excellent drug for the therapy of muscle hyperactivity disorders, such as dystonia, spasticity, and many other movement disorders. BoNTs are also effective in inhibiting both the release of ACh at sites other than NMJ and the release of neurotransmitters other than ACh. Furthermore, much evidence shows that BoNTs can act not only on the peripheral nervous system (PNS), but also on the central nervous system (CNS). Under this view, central changes may result either from sensory input from the PNS, from retrograde transport of BoNTs, or from direct injection of BoNTs into the CNS. The aim of this review is to give an update on available data, both from animal models or human studies, which suggest or confirm central alterations induced by peripheral or central BoNTs treatment. The data will be discussed with particular attention to the possible therapeutic applications to pathological conditions and degenerative diseases of the CNS.

Section: Introductionmentioning

confidence: 99%

Botulinum Neurotoxins in Central Nervous System: An Overview from Animal Models to Human Therapy

Luvisetto

2021

“…Apart from the review by Shackleton et al [28], systematic reviews on the subject have not addressed the need to consider BoNT-A's potential as first-line treatment. Given, however, that this study again finds that BoNT-A is effective in reducing pain and is seemingly durable without side effects, we conclude that an important armamentarium of neuropathic pain has languished [38,39]. For the rehabilitation medicine physicians engaged in neurorehabilitation, this is a major disadvantage given the current limiting success rates with standard treatments in pain management and the possibility that NP is likely to become a pathological condition for many patients.…”

Section: Discussionmentioning

confidence: 76%

A Systematic Review and Meta-Analysis of Efficacy of Botulinum Toxin A for Neuropathic Pain

Gupta

Edwards

Smith

et al. 2022

We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep outcomes. We conducted a Cochrane Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria analysis of RCTs from the following data sources: EMBASE, CINAHL, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane database, Cochrane Clinical Trial Register, Australia New Zealand Clinical Trials Registry, and EU Clinical Trials Register. Meta-analysis of 17 studies showed a mean final VAS reduction in pain in the intervention group of 2.59 units (95% confidence interval: 1.79, 3.38) greater than the mean for the placebo group. The overall mean difference for sleep, Hospital Anxiety and Depression Scale (HADS) anxiety, HADS depression, and QOL mental and physical sub-scales were, respectively, 1.10 (95% CI: −1.71, 3.90), 1.41 (95% CI: −0.61, 3.43), −0.16 (95% CI: −1.95, 1.63), 0.85 (95% CI: −1.85, 3.56), and −0.71 (95% CI: −3.39, 1.97), indicating no significance. BoNT-A is effective for NP; however, small-scale RCTs to date have been limited in evidence. The reasons for this are discussed, and methods for future RCTs are developed to establish BoNT-A as the first-line agent.

“…In addition, BTX-A has also been shown to effectively alleviate neuropathic pain in several animal studies. Pain relief for neuralgia occurred because BTX-A inhibited the secretion of neurotransmitters involved in pain mechanisms (protein P mediators or the nerve ending and dorsal root ganglia’s glutamate and calcitonin genes) or processes (reducing inflammation around nerve endings or deactivating sodium channels) [ 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Botulinum Toxin Type-A (Botulax®) Treatment in Patients with Intractable Chronic Occipital Neuralgia: A Pilot Study

Kim

Jang

Kim

2021

Intractable chronic occipital neuralgia (ON) is an uncommon type of headache often experienced by patients in outpatient neurological clinics. Among patients unresponsive to oral neuralgia medications, needling or injections with several drugs were suggested alternatives for treating chronic ON. This study aimed to determine the effectiveness and safety of botulinum toxin type-A (BTX-A) injection treatments, where eight patients with unilateral chronic ON received BTX-A injections at the pain sites. The pain relief effect was observed 2 weeks after receiving the injections, gradually showing improvements up to 12 weeks after injection. There were no adverse events or changes from baseline in serologic studies and vital signs in any of the participants. The treatment’s pain-relieving effects were confirmed through regular, 12-week follow-ups, confirming the safety and effectiveness of BTX-A on chronic ON and suggesting that this method is an effective, novel alternative option for chronic ON treatment.