{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:28:16Z","timestamp":1788560896568,"version":"build-2803163510"},"reference-count":152,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T00:00:00Z","timestamp":1442966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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 \u201cglamour\u201d 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.<\/jats:p>","DOI":"10.3390\/toxins7093818","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T12:24:25Z","timestamp":1443011065000},"page":"3818-3844","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1399-2152","authenticated-orcid":false,"given":"Siro","family":"Luvisetto","sequence":"first","affiliation":[{"name":"National Research Council (CNR) of Italy, Institute of Cell Biology and Neurobiology,  Roma 00185, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parisa","family":"Gazerani","sequence":"additional","affiliation":[{"name":"Center for Sensory-Motor Interaction, Department of Health Science and Technology,  Faculty of Medicine, Aalborg University, Aalborg East 9220, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Cianchetti","sequence":"additional","affiliation":[{"name":"Former Professor of Child & Adolescent Neuropsychiatry, University of Cagliari, Cagliari 09124, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaminia","family":"Pavone","sequence":"additional","affiliation":[{"name":"National Research Council (CNR) of Italy, Institute of Cell Biology and Neurobiology,  Roma 00185, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.toxicon.2013.02.014","article-title":"The life history of a botulinum toxin molecule","volume":"68","author":"Simpson","year":"2013","journal-title":"Toxicon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nrmicro3295","article-title":"Botulinum neurotoxins: Genetic, structural and mechanistic insights","volume":"12","author":"Rossetto","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/(SICI)1097-4598(199806)21:6<701::AID-MUS1>3.0.CO;2-B","article-title":"Clinical spectrum of botulism","volume":"21","author":"Cherington","year":"1988","journal-title":"Muscle Nerve"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/infdis\/jit450","article-title":"Molecular characterization of a novel botulinum neurotoxin type H gene","volume":"209","author":"Dover","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1152\/physrev.2000.80.2.717","article-title":"Neurotoxins affecting neuroexocytosis","volume":"80","author":"Schiavo","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0072-9752(07)01511-4","article-title":"Chapter 11 botulism","volume":"91","author":"Johnson","year":"2008","journal-title":"Handb. Clin. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.tibs.2014.08.009","article-title":"Botulinum neurotoxins: New questions arising from structural biology","volume":"39","author":"Kammerer","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.pharmtox.44.101802.121554","article-title":"Identification of the major steps in botulinum toxin action","volume":"44","author":"Simpson","year":"2004","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0959-4388(00)00098-2","article-title":"Structural insights into the molecular mechanism of Ca2+-dependent exocytosis","volume":"10","author":"Brunger","year":"2000","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev.neuro.26.041002.131412","article-title":"The synaptic vesicle cycle","volume":"27","author":"Sudhof","year":"2004","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00018-013-1380-7","article-title":"The blockade of the neurotransmitter release apparatus by botulinum neurotoxins","volume":"71","author":"Pantano","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1126\/science.103.2681.613","article-title":"The purification and crystallization of Clostridium botulinum type A toxin","volume":"103","author":"Lamanna","year":"1946","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0021-9258(17)35027-5","article-title":"The elemental and amino acid composition of crystalline Clostridium botulinum type A toxin","volume":"169","author":"Buehler","year":"1947","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1113\/jphysiol.1954.sp005067","article-title":"The action of botulinum toxin on motor-nerve filaments","volume":"123","author":"Brooks","year":"1954","journal-title":"J. Physiol."},{"key":"ref_15","first-page":"734","article-title":"Botulinum toxin injection of eye muscles to correct strabismus","volume":"79","author":"Scott","year":"1981","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.1002\/(SICI)1097-4598(1997)6+<129::AID-MUS9>3.0.CO;2-B","article-title":"Botulinum Toxin: Historical Perspective and Potential New Indications","volume":"20","author":"Jankovic","year":"1997","journal-title":"Muscle Nerve"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1002\/mds.20003","article-title":"Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin","volume":"19","author":"Erbguth","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0300-9084(00)00216-9","article-title":"How botulinum and tetanus neurotoxins block neurotransmitter release","volume":"82","author":"Humeau","year":"2000","journal-title":"Biochimie"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"683","DOI":"10.3390\/toxins2040683","article-title":"Bacterial toxins and the nervous system: Neurotoxins and multipotential toxins interacting with neuronal cells","volume":"2","author":"Popoff","year":"2010","journal-title":"Toxins"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.coph.2004.12.006","article-title":"Botulinal neurotoxins: Revival of an old killer","volume":"5","author":"Montecucco","year":"2005","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.parkreldis.2006.06.002","article-title":"Botulinum toxin: Clinical use","volume":"12","author":"Truong","year":"2006","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/ncpneuro0948","article-title":"Botulinum neurotoxins in the treatment of refractory pain","volume":"4","author":"Jabbari","year":"2008","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1001\/archotol.1993.01880210108015","article-title":"Botulinum toxin for the treatment of hyperfunctional lines of the face","volume":"119","author":"Blitzer","year":"1993","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_24","first-page":"241","article-title":"Botulinum toxin type A (BTX-A) for migraine: An open label assessment","volume":"13","author":"Binder","year":"1998","journal-title":"Mov. Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1067\/mhn.2000.110960","article-title":"Botulinum toxin type A (BOTOX) for treatment of migraine headaches: An open-label study","volume":"123","author":"Binder","year":"2000","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"International Headache Society (IHS) (2013). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia, 33, 679\u2013808.","DOI":"10.1177\/0333102413485658"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev-physiol-030212-183717","article-title":"Pathophysiology of migraine","volume":"75","author":"Pietrobon","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S1474-4422(09)70090-0","article-title":"Origin of pain in migraine: Evidence for peripheral sensitization","volume":"8","author":"Olesen","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1177\/0333102412449930","article-title":"The role of the neurovascular scalp structures in migraine","volume":"32","author":"Cianchetti","year":"2012","journal-title":"Cephalalgia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1526-4610.2011.01844.x","article-title":"The extracranial vascular theory of migraine\u2014A great story confirmed by the facts","volume":"51","author":"Shevel","year":"2011","journal-title":"Headache"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/bmj.39412.705868.AD","article-title":"Tension-type headache","volume":"336","author":"Loder","year":"2008","journal-title":"Br. Med. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1750-1172-3-20","article-title":"Cluster headache","volume":"3","author":"Leroux","year":"2008","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_33","first-page":"599","article-title":"Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm","volume":"50","author":"Brin","year":"1988","journal-title":"Adv. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1002\/1531-8257(199911)14:6<1043::AID-MDS1026>3.0.CO;2-3","article-title":"Painful cervical dystonia: Clinical features and response to treatment with botulinum toxin","volume":"14","author":"Tarsy","year":"1999","journal-title":"Mov. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1054\/jpai.2003.435","article-title":"Temporal relationship of muscle weakness and pain reduction in subjects treated with botulinum toxin A","volume":"4","author":"Freund","year":"2003","journal-title":"J. Pain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1177\/0333102409351807","article-title":"Measurement of vasoactive neuropeptides in biological materials: Problems and pitfalls from 30 years of experience and novel future approaches","volume":"30","author":"Edvison","year":"2010","journal-title":"Chephalalgia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrneurol.2010.127","article-title":"CGRP and its receptors provide new insights into migraine pathophysiology","volume":"6","author":"Ho","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.npep.2013.10.006","article-title":"Cortical spreading depression and calcitonin gene-related peptide: A brief review of current progress","volume":"47","author":"Wang","year":"2013","journal-title":"Neuropeptides"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1111\/head.12179","article-title":"Calcitonin gene-related peptide (CGRP) and migraine current understanding and state of development","volume":"53","author":"Bigal","year":"2013","journal-title":"Headache"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5027","DOI":"10.1016\/j.jprot.2012.06.025","article-title":"Imaging mass spectrometry to visualize biomolecule distributions in mouse brain tissue following hemispheric cortical spreading depression","volume":"75","author":"Jones","year":"2012","journal-title":"J. Proteom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.neuroscience.2013.09.002","article-title":"Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system","volume":"253","author":"Shatillo","year":"2013","journal-title":"Neuroscience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0041-0101(99)00153-1","article-title":"Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins","volume":"38","author":"Welch","year":"2000","journal-title":"Toxicon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/S0006-2952(00)00260-4","article-title":"Capsaicin-stimulated release of substance P from cultured dorsal root ganglion neurons: Involvement of two distinct mechanisms","volume":"59","author":"Purkiss","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1526-4610.2004.04007.x","article-title":"Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: Implications for migraine therapy","volume":"44","author":"Durham","year":"2004","journal-title":"Headache"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1242\/jcs.012211","article-title":"Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential","volume":"120","author":"Meng","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4981","DOI":"10.1523\/JNEUROSCI.5490-08.2009","article-title":"Activation of TRPV1 mediates calcitonin gene-related peptide release, which excites trigeminal sensory neurons and is attenuated by a retargeted botulinum toxin with anti-nociceptive potential","volume":"29","author":"Meng","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1007\/s12035-014-8665-1","article-title":"Selective cleavage of SNAREs in sensory neurons unveils protein complexes mediating peptide exocytosis triggered by different stimuli","volume":"50","author":"Meng","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e7704","DOI":"10.5812\/ircmj.7704","article-title":"Botulinum toxin type A therapy in migraine: Preclinical and clinical trials","volume":"15","author":"Shao","year":"2013","journal-title":"Iran. Red Crescent Med. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.pain.2010.07.029","article-title":"Botulinum neurotoxin type A (BoNT\/A) decreases the mechanical sensitivity of nociceptors and inhibits neurogenic vasodilation in a craniofacial muscle targeted for migraine prophylaxis","volume":"151","author":"Gazerani","year":"2010","journal-title":"Pain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"25665","DOI":"10.1074\/jbc.M311515200","article-title":"Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity","volume":"279","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/39807","article-title":"The capsaicin receptor: A heat-activated ion channel in the pain pathway","volume":"389","author":"Caterina","year":"1997","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1096\/fj.09-134346","article-title":"Differential contribution of SNARE-dependent exocytosis to inflammatory potentiation of TRPV1 in nociceptors","volume":"23","year":"2009","journal-title":"FASEB J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.nbd.2012.07.010","article-title":"Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A","volume":"48","author":"Shimizu","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/FJC.0b013e3181fd35d1","article-title":"Transient receptor potential channel activation and endothelium-dependent dilation in the systemic circulation","volume":"57","author":"Zhang","year":"2011","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s10194-011-0408-3","article-title":"Antidromic vasodilatation and the migraine mechanism","volume":"13","author":"Geppetti","year":"2012","journal-title":"J. Headache Pain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1369\/0022155413513589","article-title":"Vanilloid receptor-1 (TRPV1) expression and function in the vasculature of the rat","volume":"62","author":"Czikora","year":"2014","journal-title":"J. Histochem. Cytochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/cvr\/cvq118","article-title":"Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo","volume":"7","author":"Pozsgai","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5085","DOI":"10.1021\/jm100062h","article-title":"Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents","volume":"53","author":"Baraldi","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.toxicon.2014.12.007","article-title":"Analgesic effects of botulinum neurotoxin type A in a model of allyl isothiocyanate- and capsaicin-induced pain in mice","volume":"94","author":"Luvisetto","year":"2015","journal-title":"Toxicon"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/ncpneuro0639","article-title":"Emerging therapies for migraine","volume":"3","author":"Goadsby","year":"2007","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.molmed.2010.02.004","article-title":"TRPV1 in migraine pathophysiology","volume":"16","author":"Meents","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1136\/jnnp-2014-308813","article-title":"TRPV1, CGRP and SP in scalp arteries of patients suffering from chronic migraine","volume":"86","author":"Quartu","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00424-012-1142-7","article-title":"The role of chemosensitive afferent nerves and TRP ion channels in the pathomechanism of headaches","volume":"464","author":"Dux","year":"2012","journal-title":"Pflugers. Arch."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1129-2377-14-71","article-title":"TRPA1 and other TRP channels in migraine","volume":"14","author":"Benemei","year":"2013","journal-title":"J. Headache Pain"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1111\/bph.12512","article-title":"The TRPA1 channel in migraine mechanism and treatment","volume":"171","author":"Benemei","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1177\/0333102414527648","article-title":"Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: Therapeutic implications for migraine and other pains","volume":"34","author":"Burstein","year":"2014","journal-title":"Cephalalgia."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.neuroscience.2011.04.026","article-title":"Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin a","volume":"186","author":"Matak","year":"2011","journal-title":"Neuroscience"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.pneurobio.2014.06.001","article-title":"Botulinum toxin a, brain and pain","volume":"119\u2013120","author":"Matak","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neuropharm.2013.02.011","article-title":"Involvement of mu-opioid receptors in antinociceptive action of botulinum toxin type A","volume":"70","author":"Drinovac","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.pain.2013.06.022","article-title":"Glia and pain: Is chronic pain a gliopathy?","volume":"154","author":"Ji","year":"2013","journal-title":"Pain"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Silva, L.B., Poulsen, J.N., Arendt-Nielsen, L., and Gazerani, P. (2015). Botulinum neurotoxin type a modulates vesicular release of glutamate from satellite glial cells. J. Cell Mol. Med.","DOI":"10.1111\/jcmm.12562"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e47977","DOI":"10.1371\/journal.pone.0047977","article-title":"The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes","volume":"7","author":"Marinelli","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1124\/jpet.106.106377","article-title":"Preclinical assessment of candidate analgesic drugs: Recent advances and future challenges","volume":"319","author":"Negus","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.pain.2010.07.015","article-title":"The necessity of animal models in pain research","volume":"151","author":"Mogil","year":"2010","journal-title":"Pain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.tips.2004.04.008","article-title":"Pain-like behaviours in animals - how human are they?","volume":"25","year":"2004","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.pain.2004.09.028","article-title":"What should we be measuring in behavioral studies of chronic pain in animals?","volume":"112","author":"Mogil","year":"2004","journal-title":"Pain"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1742-7843.2004.950301.x","article-title":"Experimental human pain models: A review of standardised methods for preclinical testing of analgesics","volume":"95","author":"Staahl","year":"2004","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_78","first-page":"41","article-title":"Human experimental pain models in drug development: Translational pain research","volume":"8","author":"Curatolo","year":"2007","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1742-7843.2006.pto_211.x","article-title":"Multi-modal and tissue-differentiated experimental pain assessment: Reproducibility of a new concept for assessment of analgesics","volume":"98","author":"Staahl","year":"2006","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.jpain.2009.02.002","article-title":"Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera","volume":"10","author":"Yarnitsky","year":"2009","journal-title":"J. Pain"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1586\/ern.11.147","article-title":"Optimizing the early phase development of new analgesics by human pain biomarkers","volume":"11","author":"Hoeck","year":"2011","journal-title":"Expert Rev. Neurother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1155\/2014\/410415","article-title":"Blockade of glutamate release by botulinum neurotoxin type A in humans: A dermal microdialysis study","volume":"19","author":"Karshenas","year":"2014","journal-title":"Pain Res. Manag."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0022-510X(02)00313-1","article-title":"Botulinum toxin a and the cutaneous nociception in humans: A prospective, double-blind, placebo-controlled, randomized study","volume":"205","author":"Blersch","year":"2002","journal-title":"J. Neurol. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3390\/toxins6020592","article-title":"Time course analysis of the effects of botulinum neurotoxin type A on pain and vasomotor responses evoked by glutamate injection into human temporalis muscles","volume":"6","author":"Kulas","year":"2014","journal-title":"Toxins"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.pain.2008.10.005","article-title":"Subcutaneous botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin","volume":"141","author":"Gazerani","year":"2009","journal-title":"Pain"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.pain.2006.04.014","article-title":"The effects of botulinum toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization","volume":"122","author":"Gazerani","year":"2006","journal-title":"Pain"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s00415-003-0971-x","article-title":"Botulinum toxin a reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin","volume":"250","author":"Kramer","year":"2003","journal-title":"J. Neurol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jns.2007.03.023","article-title":"Botulinum toxin a does not alter capsaicin-induced pain perception in human skin","volume":"260","author":"Opatz","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1213\/01.ane.0000194447.46763.73","article-title":"A lack of antinociceptive or antiinflammatory effect of botulinum toxin a in an inflammatory human pain model","volume":"102","author":"Sycha","year":"2006","journal-title":"Anesth. Analg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1212\/01.WNL.0000086374.92906.6A","article-title":"A randomized, double-blind, placebo controlled study on analgesic effects of botulinum toxin a","volume":"61","author":"Voller","year":"2003","journal-title":"Neurology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.1016\/j.parkreldis.2011.06.013","article-title":"Updates on the antinociceptive mechanism hypothesis of botulinum toxin A","volume":"17","author":"Aoki","year":"2011","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.1951.sp004551","article-title":"A further survey of the action of clostridium botulinum toxin upon different types of autonomic nerve fibre","volume":"113","author":"Ambache","year":"1951","journal-title":"J. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.3390\/toxins2122890","article-title":"Botulinum neurotoxin for pain management: Insights from animal models","volume":"2","author":"Pavone","year":"2010","journal-title":"Toxins"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/ana.24122","article-title":"Botulinum toxin-a treatment reduces human mechanical pain sensitivity and mechanotransduction","volume":"75","author":"Paterson","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1124\/pr.112.006163","article-title":"Unravelling the mystery of capsaicin: A tool to understand and treat pain","volume":"64","author":"Brock","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"ref_96","first-page":"201","article-title":"Antinociceptive effect of botulinum toxin type A in rat model of carrageenan and capsaicin induced pain","volume":"46","author":"Lackovic","year":"2005","journal-title":"Croat. Med. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.pain.2006.10.030","article-title":"Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin","volume":"130","author":"Tugnoli","year":"2007","journal-title":"Pain"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.pain.2014.04.027","article-title":"Botulinum toxin type A selectivity for certain types of pain is associated with capsaicin-sensitive neurons","volume":"155","author":"Matak","year":"2014","journal-title":"Pain"},{"key":"ref_99","first-page":"203","article-title":"The UVB cutaneous inflammatory pain model: A reproducibility study in healthy volunteers","volume":"5","author":"Gazerani","year":"2013","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.pain.2012.01.003","article-title":"Comparison of glutamate-evoked pain between the temporalis and masseter muscles in men and women","volume":"153","author":"Castrillon","year":"2012","journal-title":"Pain"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"825","DOI":"10.2165\/11208880-000000000-00000","article-title":"Onabotulinumtoxina (botox\u00ae): A review of its use in the prophylaxis of headaches in adults with chronic migraine","volume":"72","author":"Frampton","year":"2012","journal-title":"Drugs"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.pain.2003.10.008","article-title":"Subcutaneous administration of botulinum toxin a reduces formalin-induced pain","volume":"107","author":"Cui","year":"2004","journal-title":"Pain"},{"key":"ref_103","first-page":"347","article-title":"Increased levels of SV2A botulinum neurotoxin receptor in clinical sensory disorders and functional effects of botulinum toxins A and E in cultured human sensory neurons","volume":"4","author":"Yiangou","year":"2011","journal-title":"J. Pain Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1097\/j.pain.0000000000000119","article-title":"OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine","volume":"156","author":"Larrosa","year":"2015","journal-title":"Pain"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.neuro.2005.01.017","article-title":"Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A","volume":"26","author":"Aoki","year":"2005","journal-title":"Neurotoxicology."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"377","DOI":"10.2217\/pmt.14.30","article-title":"Botulinum neurotoxin A for chronic migraine headaches: Does it work and how?","volume":"4","author":"Cairns","year":"2014","journal-title":"Pain Manag."},{"key":"ref_107","unstructured":"Walsh, S. (2010). FDA Approves Botox to Treat Chronic Migraine, U.S. Food and Drug Administration."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/00019052-200006000-00009","article-title":"Tension-type headache: An update on mechanisms and treatment","volume":"13","author":"Jensen","year":"2000","journal-title":"Curr. Opin. Neurol."},{"key":"ref_109","first-page":"S71","article-title":"Treatment of tension type headache by local injection of botulinum toxin","volume":"4","author":"Relja","year":"1997","journal-title":"Eur. J. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"I12","DOI":"10.1007\/s00415-004-1104-x","article-title":"Botulinum toxin in tension-type headache","volume":"251","author":"Relja","year":"2004","journal-title":"J. Neurol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1046\/j.1526-4610.2002.02234.x","article-title":"Relief of tension-type headache symptoms in subjects with temporomandibular disorders treated with botulinum toxin-A","volume":"42","author":"Freund","year":"2002","journal-title":"Headache"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1111\/j.1468-1331.1999.tb00044.x","article-title":"Prophylactic treatment of chronic tension-type headache using botulinum toxin type A","volume":"6","author":"Smuts","year":"1999","journal-title":"Eur. J. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1046\/j.1526-4610.2001.041007658.x","article-title":"Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: A double-blind, placebo controlled trial","volume":"41","author":"Schmitt","year":"2001","journal-title":"Headache"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1046\/j.1526-4610.2000.00044.x","article-title":"Treatment of tension-type headache with botulinum toxin type A: A double-blind, placebo-controlled study","volume":"40","author":"Rollnik","year":"2000","journal-title":"Headache"},{"key":"ref_115","first-page":"455","article-title":"Treatment of chronic tension-type headache with botulinum toxin","volume":"19","author":"Gobel","year":"1999","journal-title":"Cephalalgia"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1468-2982.2004.00738.x","article-title":"Treatment of chronic tension-type headache with botulinum toxin: A double-blind, placebo-controlled clinical trial","volume":"24","author":"Padberg","year":"2004","journal-title":"Cephalalgia"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.pain.2004.01.016","article-title":"Treatment of chronic tension-type headache with botulinum toxin A: A randomized, double-blind, placebo-controlled multicenter study","volume":"109","author":"Krack","year":"2004","journal-title":"Pain"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1111\/j.1468-2982.2006.01114.x","article-title":"Botulinum toxin type A in the prophylactic treatment of chronic tension-type headache: A multicentre, double-blind, randomized, placebo-controlled, parallel-group study","volume":"26","author":"Silberstein","year":"2006","journal-title":"Cephalalgia"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1001\/jama.2012.505","article-title":"Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: A meta-analysis","volume":"307","author":"Jackson","year":"2012","journal-title":"JAMA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/s10194-007-0400-0","article-title":"Botulinum toxin type-A therapy in cluster headache: An open study","volume":"8","author":"Sostak","year":"2007","journal-title":"J. Headache Pain"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s11910-014-0459-3","article-title":"The neuralgias: Diagnosis and management","volume":"14","author":"Gadient","year":"2014","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1586\/14737175.7.11.1565","article-title":"Trigeminal neuralgia: For one nerve a multitude of treatments","volume":"7","author":"Cheshire","year":"2007","journal-title":"Expert Rev. Neurother."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1054\/jpai.2002.27142","article-title":"The use of botulinum toxin for the treatment of chronic facial pain","volume":"3","author":"Borodic","year":"2002","journal-title":"J. Pain"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1212\/01.wnl.0000180940.98815.74","article-title":"An open study of botulinum-A toxin treatment of trigeminal neuralgia","volume":"65","author":"Piovesan","year":"2005","journal-title":"Neurology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/01.wnf.0000172497.24770.b0","article-title":"Botulinum toxin and intractable trigeminal neuralgia","volume":"28","author":"Ilhan","year":"2005","journal-title":"Clin. Neuropharmacol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1590\/S0004-282X2008000400012","article-title":"Beneficial effects of botulinum toxin type A in trigeminal neuralgia","volume":"66","author":"Zuniga","year":"2008","journal-title":"Arq. NeuroPsiquiatr."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.tripleo.2010.04.043","article-title":"Use of botulinum toxin A for drug-refractory trigeminal neuralgia: Preliminary report","volume":"111","author":"Bohluli","year":"2011","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/00002508-200503000-00010","article-title":"Injections of botulinum toxin type A produce pain alleviation in intractable trigeminal neuralgia","volume":"21","author":"Brown","year":"2005","journal-title":"Clin. J. Pain"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1016\/j.tripleo.2009.03.021","article-title":"Injection of botulinum toxin type A (BOTOX) into trigger zone of trigeminal neuralgia as a means to control pain","volume":"109","author":"Ngeow","year":"2010","journal-title":"Oral Surg., Oral Med., Oral Pathol., Oral Radiol., Endod."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1177\/0333102412441721","article-title":"Botulinum toxin type A for the treatment of trigeminal neuralgias: Results from a randomized, double-blind, placebo-controlled trial","volume":"32","author":"Wu","year":"2012","journal-title":"Cephalgia"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1129-2377-15-65","article-title":"Two doses of botulinum toxin type A for the treatment of trigeminal neuralgia: Observation of therapeutic effect from a randomized, double-blind, placebo-controlled trial","volume":"15","author":"Zhang","year":"2014","journal-title":"J. Headache Pain."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/1129-2377-14-92","article-title":"Botulinum toxin-type A: Could it be an effective treatment option in intractable trigeminal neuralgia?","volume":"14","author":"Shehata","year":"2013","journal-title":"J. Headache Pain"},{"key":"ref_133","first-page":"1","article-title":"Botulinum Toxin A in the Treatment of Trigeminal Neuralgia","volume":"19","author":"Xia","year":"2015","journal-title":"Int. J. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/j.1468-2982.2005.00959.x","article-title":"Botulinum toxin A for the treatment of greater occipital neuralgia and trigeminal neuralgia: A case report with pathophysiological considerations","volume":"26","author":"Volcy","year":"2006","journal-title":"Cephalalgia."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1533-2500.2007.00150.x","article-title":"Botulinum toxin occipital nerve block for the treatment of severe occipital neuralgia: A case series","volume":"7","author":"Kapural","year":"2007","journal-title":"Pain Pract."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1111\/j.1526-4610.2008.01089.x","article-title":"Botulinum toxin type-a (botox) in the treatment of occipital neuralgia: A pilot study","volume":"48","author":"Taylor","year":"2008","journal-title":"Headache"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1111\/bph.12763","article-title":"Therapeutic use of botulinum toxin in migraine: Mechanism of action","volume":"171","author":"Ramachandran","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1212\/01.wnl.0000311390.87642.d8","article-title":"Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): Report of the therapeutics and technology assessment subcommittee of the american academy of neurology","volume":"70","author":"Naumann","year":"2008","journal-title":"Neurology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1177\/0333102410364676","article-title":"PREEMPT 1 Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: Results from the doubleblind, randomized, placebo-controlled phase of the PREEMPT 1 trial","volume":"30","author":"Aurora","year":"2010","journal-title":"Cephalalgia"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1177\/0333102410364677","article-title":"PREEMPT 2 Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: Results from the doubleblind, randomized, placebo-controlled phase of the PREEMPT 2 trial","volume":"30","author":"Diener","year":"2010","journal-title":"Cephalalgia"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/j.1526-4610.2010.01678.x","article-title":"Onabotulinumtoxina for treatment of chronic migraine: Pooled results from the double-blind, randomized, placebo-controlled phases of the preempt clinical program","volume":"50","author":"Dodick","year":"2010","journal-title":"Headache"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jns.2013.05.003","article-title":"Onabotulinumtoxina for treatment of chronic migraine: Preempt 24-week pooled subgroup analysis of patients who had acute headache medication overuse at baseline","volume":"331","author":"Silberstein","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/ane.12171","article-title":"OnabotulinumtoxinA for chronic migraine: Efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program","volume":"129","author":"Aurora","year":"2014","journal-title":"Acta. Neurol. Scand."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1212\/WNL.82.10_supplement.P7.186","article-title":"The Durability of OnabotulinumtoxinA for the Treatment of Chronic Migraine: CLARITY Pilot Study (P7.186)","volume":"82","author":"Blumenfeld","year":"2014","journal-title":"Neurology"},{"key":"ref_145","first-page":"654","article-title":"Rationale for study and design of COMPEL: An open-Label, multicenter study of the long-term efficacy, safety, and tolerability of onabotulinumtoxinA for headache prophylaxis in adults with chronic migraine","volume":"3","author":"Blumenfeld","year":"2012","journal-title":"F1000Posters"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1212\/WNL.84.14_supplement.P1.306","article-title":"Efficacy and Safety of OnabotulinumtoxinA in a Long-Term, Open-Label Study for the Prophylaxis of Headaches in Adult Chronic Migraine Patients: An Interim Analysis of the COMPEL Study (P1.306)","volume":"84","author":"Blumenfeld","year":"2015","journal-title":"Neurology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1177\/0333102414561873","article-title":"Long-term experience with onabotulinumtoxinA in the treatment of chronic migraine: What happens after one year?","volume":"35","author":"Larrosa","year":"2015","journal-title":"Cephalalgia"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1046\/j.1526-4610.2003.03167.x","article-title":"Procedures for administering botulinum toxin type A for migraine and tension-type headache","volume":"43","author":"Blumenfeld","year":"2003","journal-title":"Headache"},{"key":"ref_149","unstructured":"Silberstein, S.D. (2009). Botulinum. Toxin: Therapeutic Clinical Practice and Science, Saunders."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1111\/j.1526-4610.2010.01766.x","article-title":"Method of injection of onabotulinumtoxina for chronic migraine: A safe, well-tolerated, and effective treatment paradigm on the preempt clinical program","volume":"50","author":"Blumenfeld","year":"2010","journal-title":"Headache"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Jabbari, B. (2015). Botulinum. Toxin Treatment of Pain Disorders, Springer Publisher.","DOI":"10.1007\/978-1-4939-2501-8"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1136\/jnnp-2014-309295","article-title":"TRPV1, CGRP and SP in scalp arteries of patients suffering from chronic migraine. Some like it hot! Chronic migraine increases TRPV1 receptors in the scalp","volume":"86","author":"Silberstein","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatr."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/9\/3818\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:49:09Z","timestamp":1760215749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/9\/3818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,23]]},"references-count":152,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,9]]}},"alternative-id":["toxins7093818"],"URL":"https:\/\/doi.org\/10.3390\/toxins7093818","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,23]]}}}