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The traditional mechanism described for onabotulinumtoxinA \u2013 reducing muscle contractions \u2013 is insufficient to explain its efficacy in migraine, which is primarily a sensory neurological disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A narrative literature review on the mechanism of action of onabotulinumtoxinA in chronic migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Following injection into tissues, onabotulinumtoxinA inhibits soluble N\u2010ethylmaleimide\u2010sensitive fusion attachment protein receptor (SNARE)\u2010mediated vesicle trafficking by cleaving one of its essential proteins, soluble N\u2010ethylmaleimide\u2010sensitive fusion attachment protein (SNAP\u201025), which occurs in both motor and sensory nerves. OnabotulinumtoxinA inhibits regulated exocytosis of motor and sensory neurochemicals and proteins, as well as membrane insertion of peripheral receptors that convey pain from the periphery to the brain, because both processes are SNARE dependent. OnabotulinumtoxinA can decrease exocytosis of pro\u2010inflammatory and excitatory neurotransmitters and neuropeptides such as substance P, calcitonin gene\u2010related peptide, and glutamate from primary afferent fibers that transmit nociceptive pain and participate in the development of peripheral and central sensitization. OnabotulinumtoxinA also decreases the insertion of pain\u2010sensitive ion channels such as transient receptor potential cation channel subfamily V member 1 (TRPV1) into the membranes of nociceptive neurons; this is likely enhanced in the sensitized neuron. For chronic migraine prevention, onabotulinumtoxinA is injected into 31\u201039 sites in 7 muscles of the head and neck. Sensory nerve endings of neurons whose cell bodies are located in trigeminal and cervical ganglia are distributed throughout the injected muscles, and are overactive in people with migraine. Through inhibition of these sensory nerve endings, onabotulinumtoxinA reduces the number of pain signals that reach the brain and consequently prevents activation and sensitization of central neurons postulated to be involved in migraine chronification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>OnabotulinumtoxinA likely acts via sensory mechanisms to treat chronic migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.13849","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T08:56:05Z","timestamp":1593507365000},"page":"1259-1272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":195,"title":["Mechanism of Action of OnabotulinumtoxinA in Chronic Migraine: A Narrative Review"],"prefix":"10.1111","volume":"60","author":[{"given":"Rami","family":"Burstein","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine Beth Israel Deaconess Medical Center Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Blumenfeld","sequence":"additional","affiliation":[{"name":"The Headache Center of Southern California The Neurology Center Carlsbad CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Silberstein","sequence":"additional","affiliation":[{"name":"Department of Neurology Jefferson Headache Center Thomas Jefferson University Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey","family":"Manack Adams","sequence":"additional","affiliation":[{"name":"Allergan, Inc. 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