title: Botulinum Toxin Type a as a Therapeutic Agent against Headache and Related Disorders.
abstract: 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.
authors.affiliation: National Research Council (CNR) of Italy, Institute of Cell Biology and Neurobiology, Roma 00185, Italy. siro.luvisetto@cnr.it.
authors.forename: Siro
authors.initials: S
authors.lastname: Luvisetto
authors.affiliation: Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg East 9220, Denmark. gazerani@hst.aau.dk.
authors.forename: Parisa
authors.initials: P
authors.lastname: Gazerani
authors.affiliation: Former Professor of Child & Adolescent Neuropsychiatry, University of Cagliari, Cagliari 09124, Italy. cianchet@unica.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cianchetti
authors.affiliation: National Research Council (CNR) of Italy, Institute of Cell Biology and Neurobiology, Roma 00185, Italy. flaminia.pavone@cnr.it.
authors.forename: Flaminia
authors.initials: F
authors.lastname: Pavone
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004421:Dystonia / Q000188:drug therapy; D006261:Headache / Q000188:drug therapy*; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy; D009128:Muscle Spasticity / Q000188:drug therapy; D009437:Neuralgia / Q000188:drug therapy; D009465:Neuromuscular Agents / Q000737:chemistry / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A
keywords: animal pain model; botulinum toxin; cephalalgias; clinical trials; cluster headache; headache; human pain model; migraine; tension-type headache