OnabotulinumtoxinA for trigeminal neuralgia: a review of the available data
Trigeminal neuralgia (TN) patients may develop side effects from centrally acting drugs, have contraindications for neurosurgical procedures, or experience relapse during conventional therapies. OnabotulinumtoxinA (BoNT/A) has been reported to be effective for TN, although this finding has been challenged. An overview of the available evidence based on a narrative/qualitative analysis of the literature is presented. About 90% of patients who receive BoNT/A show an improvement, a higher figure than that reported for the placebo effect of BoNT/A for other headaches. Tolerability of BoNT/A is good, and its few side-effects are transient. The articles reviewed were mainly case reports, case series and open-label trials; however, randomized controlled trials have endorsed the efficacy of BoNT/A for TN. This evidence, together with a better understanding of the analgesic mechanisms of BoNT/A and its proven efficacy in treating other pain syndromes, supports the use of this toxin as a therapeutic option for TN.
Key words: trigeminal neuralgia; botulinum neurotoxin type A; botulinum-A toxin; onabotulinumtoxin A; neuropathic pain
Neurobiological mechanisms responsible for the antinociceptive activity of BoNT/A
After being injected in the subcutaneous tissue, BoNT/A is taken up by endocytosis at nerve terminals of C fibers and rises by retrograde axonal transport through the trigeminal ganglion to the spinal trigeminal nucleus46. One of the main antinociceptive effects of BoNT/A is probably related to its ability to block the transport of nociceptive input to centers modulating nociception43.
BoNT/A negatively modulates nociceptive neurotransmitters. Its action can be preganglionic, on CGRP47,48,49, substance P50 and glutamate51, or postganglionic, on synaptic terminations, blocking the release of norepinephrine (NE) and adenosine triphosphate (ATP)52,53. A third mechanism may involve internal and external sensory adaptation. In external neural adaptation, BoNT/A reduces secretion of neuroeffector substances from mast cells, blood vessel endothelium and sensory nerve tissue54.
One of the main mechanisms responsible for the antinociceptive action of BoNT/A in the treatment of trigeminal neuralgia may be its ability to modulate intrinsic sensory adaptation (by controlling vesicular traffic), which it does by acting directly on transient receptor potential (TRP) ion channels. The TRPs act as integrators of several stimuli and signaling pathways. Dysfunction of these channels contributes to thermal hyperalgesia and allodynia under painful pathological conditions such as trigeminal neuropathy. Among these receptors, those that can potentially be used to treat trigeminal neuralgia include TRPV1, TRPV2, TRPV4, TRPM3, TRPM8 and TRPA155. The vanilloid receptor TRPV1 is potentially inhibited after injection of BoNT/A in the region of the first trigeminal branch56. The effect of BoNT/A on TRPV1 expression in trigeminal neuralgia leads to reduced expression of CGRP and satisfactory control of facial pain49. When blocked, TRPA1 provides a satisfactory reduction in facial mechanical allodynia and cold hyperalgesia57,58. To date, no studies showing the effect of BoNT/A on TRPA1 have been published.
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