Botulinum Toxin Treatment of Neuropathic Pain

Abstract

Neuropathic pain (NP), a common form of human pain, often poorly responds to analgesic medications. In this review the authors discuss the pathophysiology and conventional treatment of neuropathic pain and provide evidenced-based statements on the efficacy of botulinum neurotoxins (BoNTs) in this form of pain. The level of efficacy for BoNT treatment in each category of NP is defined according to the published guidelines of the American Academy of Neurology. The data indicate that BoNT treatment (most of the literature is with onabotulinumtoxinA) is effective (level A evidence) in postherpetic neuralgia and trigeminal neuralgia. It is probably effective (level B) in posttraumatic neuralgia and painful diabetic neuropathy. The data on complex regional pain syndrome, carpal tunnel syndrome, occipital neuralgia, and phantom limb pain are preliminary and await conduction of randomized, blinded clinical trials. Much remains to be learned about the most-effective dosage and technique of injection, optimum dilutions, and differences among BoNTs in the treatment of neuropathic pain.

Intramuscular Botulinum toxin A injections induce central changes to axon initial segments and cholinergic boutons on spinal motoneurones in rats

“…In addition, only the responses to single doses of BoNT/A have been investigated in the current study and so it will be important in the future to investigate the long-term consequence of repeated injections. This is highly relevant as BoNT/A is increasingly being recommended for the treatment of a number of clinical disorders in which increased neuronal excitability is involved including idiopathic over-active bladder 42 , hemifacial spasms, cervical dystonia, various dyskinesias and spasticity following traumatic brain injury (reviewed by 43 ) and even for conditions such as migraine 44 and chronic pain 45 . BoNT/A is also currently being used in younger patients, most notably in children with cerebral palsy 46 .…”

Botulinum Neurotoxins and Cancer—A Review of the Literature

“…The inhibitory effect of the BoNTs upon the release of acetylcholine at the neuromuscular junction is mostly responsible for the relief of pain caused by muscle spasms. In the case of neuropathic pain, it is currently believed that the analgesic effect of botulinum injections predominantly results from inhibition of pain neurotransmitters both at peripheral and at central sensory levels [5,6,71,72]. The peripheral injection of botulinum toxin-A into the muscle or close to peripheral nerve endings reduces the release of calcitonin gene related peptide, a major pain transmitter from trigeminal ganglion [73].…”

Botulinum Toxin in Restless Legs Syndrome—A Randomized Double-Blind Placebo-Controlled Crossover Study

“…This is the primary reason it helps in conditions such as spasticity, cervical dystonia, blepharospasm, hemifacial spasm, and focal dystonias. BoNTs also alleviate neuropathic pain in animals through several mechanisms: blocking the release of pain mediators (glutamate, substance P, calcitonin gene related peptide (CRGP)) from peripheral terminals, dorsal root ganglia (DRG), and spinal cord neurons; decreasing local inflammation around nerve terminals; deactivation of sodium channels and decreasing sympathetic transmission [ 13 ]. Thus, there is an expanding literature on the role of BoNTs in pain conditions such as chronic migraine, post herpetic neuralgia, post-traumatic neuralgia, trigeminal neuralgia, and other neuropathic pain conditions.…”

“…These studies demonstrated mixed results with an unclear consensus. There is evidence that BoNTs may modulate afferent sensory fiber firing and thereby reduce the central sensitization and pain perception [ 13 ]. To date, the present trial is the largest double-blinded placebo-controlled study assessing the efficacy and safety of botulinum neurotoxin type A, namely incobotulinumtoxinA (IncoA) in refractory RLS patients.…”