Botulinum neurotoxin type A for the treatment of pain: not just in migraine and trigeminal neuralgia

Giorgio Sandrini, Roberto De Icco, Cristina Tassorelli, Nicola Smania, Stefano Tamburin, Giorgio Sandrini, Roberto De Icco, Cristina Tassorelli, Nicola Smania, Stefano Tamburin

Abstract

Background: Despite their huge epidemiological impact, primary headaches, trigeminal neuralgia and other chronic pain conditions still receive suboptimal medical approach, even in developed countries. The limited efficacy of current pain-killers and prophylactic treatments stands among the main reasons for this phenomenon. Botulinum neurotoxin (BoNT) represents a well-established and licensed treatment for chronic migraine, but also an emerging treatment for other types of primary headache, trigeminal neuralgia, neuropathic pain, and an increasing number of pain conditions.

Methods: We searched and critically reviewed evidence for the efficacy of BoNT for the treatment of chronic pain.

Results: Meta-analyses and randomized controlled trials (RCTs) suggest that BoNT potentially represents a multi-purpose drug for the treatment of pain in several disorders due to a favorable safety profile and a long-lasting relief after a single injection.

Conclusions: BoNT is an emerging treatment in different pain conditions. Future RCTs should explore the use of BoNT injection therapy combined with systemic drugs and/or physical therapies as new pain treatment strategies.

Keywords: Botulinum neurotoxin; Migraine; Neuropathic pain; Pain; Primary headaches; Treatment; Trigeminal neuralgia.

Figures

Fig. 1
Fig. 1
The neurobiological mechanisms of the effect of botulinum neurotoxin (BonT) on pain according to animal models [16] and the anatomical levels where they may take place. Panel a shows a normal axon and the role of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, here represented by a chain, for allowing the fusion between the synaptic vescicles (red circles) containing a neurotransmitter (black dots) and the axonal membrane resulting in the neurotransmitter release. Panel b shows the effect of the BoNT, represented by scissors that cleave the SNARE complex and impede vescicle fusion and neurotransmitter release. Panel c shows peripheral sensitization after tissue injury, which results in the release of a number of inflammatory mediators (e.g., histamine, bradykinin, prostaglandins, interleukins, adenosine, and nerve growth factors) that, in turn, induce the expression of transient receptor potential (TRP) channels and cause sensitization of the peripheral nociceptor. BoNT may cleave the SNARE complex, block fusion of the vescicles (blue circles) containing TRP channels (white dots) and reduce peripheral nociceptor sensitization. This mechanism may contribute to the effect of BoNT on nociceptive pain and peripheral neuropathic pain (NP). Panel d shows retrograde axonal transport of BoNT to the dorsal horn of the spinal cord where it can block the release of pain-modulating neurotransmitters, such as glutamate, substance P, and calcitonin gene-related peptide (CGRP). This mechanism may reduce central sensitization phenomena and spinal NP

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