Botulinum neurotoxin A for chronic migraine headaches: does it work and how?

Cairns, Brian E.; Gazerani, Parisa

doi:10.2217/pmt.14.30

Cited by 9 publications

(8 citation statements)

References 21 publications

(27 reference statements)

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“…This evidence in humans is supported by animal experiments where nociceptive evoked response amplitude was sensitive to the pharmacological modulation of trigeminal activation [ 22 , 23 ]. Apart from the well-known direct action of BontA in attenuating nociceptive input from the muscles [ 24 ], it has also been proposed that, when injected peripherally, it can access the CNS, decreasing synaptic transmission in pain pathways [ 10 ]. It was supposed on the basis of several evidences that internalization of the neurotoxin in the sensory nerves that innervates the muscles and the skin, would result in a central effect by blocking CGRP and Glutamate in the spinal cord, thus inhibiting second order neuron transmission [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…Apart from the inhibition of the release of acetylcholine, resulting in muscle paralysis, the internalization of the neurotoxin in sensory neurons that innervate the skin and muscles could potentially inhibit the release of pro-inflammatory mediators at several sites within the sensory neuron and suppress neurogenic inflammation near the injection site by preventing the release of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P from free nerve endings [ 7 , 8 ]. In addition, the neurotoxin can exert a modulating effect on central sensitization by blocking the release of CGRP and glutamate from nociceptive nerve fibers terminating in the spinal cord, thus suppressing the stimulation of second-order neurons and glial cells [ 4 , 9 , 10 , 11 ]. The role of CGRP and glutamate in chronic migraine pathophysiology and related phenomena of central sensitization is supported by numerous evidences [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Effects of OnabotulintoxinA on Habituation of Laser Evoked Responses in Chronic Migraine

Tommaso

Delussi

Ricci

et al. 2016

Toxins

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Onabotulintoxin A (BontA) is an efficacious preventive treatment for chronic migraine, though the specific mechanism of action is still under discussion. The study aims: (1) To evaluate pain processing modifications in chronic migraine patients (CM) under single BontA administration in pericranial muscles, by means of CO2 Laser Evoked Potentials (LEPs) obtained by the stimulation of the skin over the right frontal and trapezius injection sites and hand dorsum, in a double blind placebo controlled crossover design. (2) To correlate main LEPs findings with clinical outcome after one year of BontA treatment. Twenty refractory CM patients were included in the analysis. The LEPs were recorded in basal conditions and seven days after BontA (PREEMPT protocol) and saline solution injection. The N1, N2 and P2 amplitude and latencies and N2P2 habituation index were evaluated and correlated with the percent change of headache frequency after one year of toxin treatment. After seven days of BontA treatment, a normalization of the trigeminal habituation index was observed, which was correlated with the clinical outcome after one year of BontA therapy. Patients displaying trigeminal LEPs facilitation at T0 time showed a more efficient therapeutic outcome. Neurotoxin may exert a modulating effect on trigeminal nociception, normalizing central neurotransmission.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of OnabotulintoxinA on Habituation of Laser Evoked Responses in Chronic Migraine

Tommaso

Delussi

Ricci

et al. 2016

Toxins

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show abstract

“…CGRP levels after BoNT/A treatment were significantly lower as compared to CGRP levels before BoNT/A treatment. Blocking the release of these neurotransmitters inhibits neurogenic inflammation and peripheral sensitization, which potentially blocks the development of central sensitization [ 91 , 105 , 106 ].…”

Section: Bont/a and Headache: Is Bont/a Effective At Treating Painmentioning

confidence: 99%

Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

Luvisetto

Gazerani

Cianchetti

et al. 2015

Toxins

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Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.

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“…Furthermore duration of effect appears to be different between smooth and skeletal muscle. Other disciplines have confirmed its complex mode of action, and its effective use in painful conditions such as chronic migraine headaches and cervical dystonia further supports sensory effects of the toxin . There has been a significant publication base in this area in recent years and some of the key findings and controversies related to the bladder are highlighted below.…”

Section: Mechanism Of Action (Moa) Of Botulinum Toxin a (Bont/a) Whenmentioning

confidence: 97%

Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder? ICI-RS 2014

Apostolidis

Rahnama’i

Fry

et al. 2016

Neurourol. Urodynam.

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The mechanism of action of BoNT/A in the bladder is complex and not fully understood. There is emerging support for its role on afferent mechanisms. The technical aspects of the injection procedure have been standardized to a certain extent but further study is required in larger scale studies to assess minimizing voiding dysfunction, improving tolerability, and assessing alternatives to injections.

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Botulinum neurotoxin A for chronic migraine headaches: does it work and how?

Cited by 9 publications

References 21 publications

Effects of OnabotulintoxinA on Habituation of Laser Evoked Responses in Chronic Migraine

Effects of OnabotulintoxinA on Habituation of Laser Evoked Responses in Chronic Migraine

Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder? ICI-RS 2014

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