{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:27:05Z","timestamp":1791872825260,"version":"4.3.4"},"reference-count":133,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"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>OnabotulinumtoxinA (BT-A) is used in different medical fields for its beneficial effects. BT-A, a toxin originally produced by the bacterium Clostridium botulinum, is widely known for its ability to temporarily paralyze muscles by blocking the release of acetylcholine, a neurotransmitter involved in muscle contraction. The literature continually reports new hypotheses regarding potential applications that do not consider blockade of acetylcholine release at the neuromuscular junction as a common pathway. In this opinion article, it is our aim to investigate the different pathway targets of BT-A in different medical applications. First of all, the acetylcholine effect of BT-A is used to reduce wrinkles for cosmetic purposes, in the treatment of urological problems, excessive sweating, temporomandibular joint disorders, obesity, migraine, spasticity in neurological diseases, and in various cases of muscle overactivity such as cervical dystonia, blepharospasm, and essential head tremor. In another potential pathway, glutamate A, CGRP, and substance P are targeted for pain inhibition with BT-A application in conditions such as migraine, trigeminal neuralgia, neuropathic pain, and myofascial pain syndrome. On the other hand, as a mechanism different from acetylcholine and pain mediators, BT-A is used in the treatment of hair loss by increasing oxygenation and targeting transforming growth factor-beta 1 cells. In addition, the effect of BT-A on the apoptosis of cancer cells is also known and is being developed. The benefits of BT-A applied in different doses to different regions for different medical purposes are shown in literature studies, and it is also emphasized in those studies that repeating the applications increases the benefits in the long term. The use of BT-A continues to expand as researchers discover new potential therapeutic uses for this versatile toxin.<\/jats:p>","DOI":"10.3390\/toxins16070309","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T07:57:45Z","timestamp":1720425465000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9505-6135","authenticated-orcid":false,"given":"Dilara","family":"Onan","sequence":"first","affiliation":[{"name":"Department of Physiotherapy and Rehabilitation, Faculty of Heath Sciences, Yozgat Bozok University, Yozgat 66000, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Farham","sequence":"additional","affiliation":[{"name":"Department of Headache, Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran 1417653761, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-4128","authenticated-orcid":false,"given":"Paolo","family":"Martelletti","sequence":"additional","affiliation":[{"name":"School of Health, Unitelma Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1212\/WNL.53.8.1850","article-title":"Historical aspects of botulinum toxin: Justinus Kerner (1786\u20131862) and the \u201csausage poison\u201d","volume":"53","author":"Erbguth","year":"1999","journal-title":"Neurology"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"e32372","DOI":"10.1097\/MD.0000000000032372","article-title":"Botox [onabotulinumtoxinA] mechanism of action","volume":"102","author":"Brin","year":"2023","journal-title":"Medicine"},{"key":"ref_4","first-page":"701","article-title":"Classics in infectious diseases. A new anaerobic bacillus and its relation to botulism. E. van Ermengem. Originally published as \u201cUeber einen neuen ana\u00ebroben Bacillus und seine Beziehungen zum Botulismus\u201d in Zeitschrift f\u00fcr Hygiene und Infektionskrankheiten 26: 1-56, 1897","volume":"1","year":"1979","journal-title":"Rev. Infect. Dis."},{"key":"ref_5","first-page":"S36","article-title":"Botulinum Toxin in Migraine Treatment","volume":"50","year":"2013","journal-title":"Noro Psikiyatr. Ars."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1046\/j.1526-4610.43.7s.4.x","article-title":"Synaptic transmission: Inhibition of neurotransmitter release by botulinum toxins","volume":"43","author":"Dolly","year":"2003","journal-title":"Headache"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.coph.2009.03.004","article-title":"Neuro-exocytosis: Botulinum toxins as inhibitory probes and versatile therapeutics","volume":"9","author":"Dolly","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0928-4257(01)00086-9","article-title":"Botulinum neurotoxins: From paralysis to recovery of functional neuromuscular transmission","volume":"96","author":"Meunier","year":"2002","journal-title":"J. Physiol. Paris"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3200","DOI":"10.1073\/pnas.96.6.3200","article-title":"Functional repair of motor endplates after botulinum neurotoxin type A poisoning: Biphasic switch of synaptic activity between nerve sprouts and their parent terminals","volume":"96","author":"Meunier","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/01.iio.0000167167.10402.74","article-title":"Pharmacology and immunology of botulinum neurotoxins","volume":"45","author":"Aoki","year":"2005","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_11","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_12","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_13","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_14","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_15","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_16","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_17","doi-asserted-by":"crossref","first-page":"I1","DOI":"10.1007\/s00415-004-1102-z","article-title":"Neurobiological basis for the use of botulinum toxin in pain therapy","volume":"251","author":"Mense","year":"2004","journal-title":"J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1213\/ANE.0b013e3181ffa1d7","article-title":"Intrathecal administration of botulinum neurotoxin type A attenuates formalin-induced nociceptive responses in mice","volume":"112","author":"Lee","year":"2011","journal-title":"Anesth. Analg."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1533-2500.2008.00202.x","article-title":"Evidence for the use of botulinum toxin in the chronic pain setting--a review of the literature","volume":"8","author":"Jeynes","year":"2008","journal-title":"Pain Pract."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00702-007-0758-9","article-title":"Future aspects of botulinum neurotoxins","volume":"115","author":"Aoki","year":"2008","journal-title":"J. Neural Transm."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"3935","DOI":"10.1113\/jphysiol.2013.255075","article-title":"SNARE proteins are essential in the potentiation of NMDA receptors by group II metabotropic glutamate receptors","volume":"591","author":"Cheng","year":"2013","journal-title":"J. Physiol."},{"key":"ref_24","unstructured":"Dysport (2024, May 28). Prescribing Information. Available online: https:\/\/www.galderma.com\/us\/sites\/default\/files\/2020-11\/1066038%20Dysport%20PI.pdf."},{"key":"ref_25","unstructured":"Botox (2024, May 28). Prescribing Information. Available online: https:\/\/www.rxabbvie.com\/pdf\/botox_pi.pdf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.jaad.2019.11.042","article-title":"Botulinum toxin: Pharmacology and injectable administration for the treatment of primary hyperhidrosis","volume":"82","author":"Nawrocki","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_27","first-page":"14","article-title":"Botulinum Toksininin Kozmetik Uygulamalar\u0131","volume":"12","author":"Dursun","year":"2019","journal-title":"T\u00fcrkiye Klinikleri Kozmetik Dermatoloji \u00d6zel Dergisi"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1600-0625.2004.00258.x","article-title":"Novel aspects in cutaneous biology of acetylcholine synthesis and acetylcholine receptors","volume":"13","author":"Kurzen","year":"2004","journal-title":"Exp Dermatol."},{"key":"ref_29","unstructured":"Biello, A., Oney, R., and Zhu, B. (2024). Botulinum Toxin Treatment of the Upper Face, StatPearls."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1111\/j.1524-4725.2012.02582.x","article-title":"OnabotulinumtoxinA: A meta-analysis of duration of effect in the treatment of glabellar lines","volume":"38","author":"Glogau","year":"2012","journal-title":"Dermatol. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1097\/DSS.0000000000003585","article-title":"High Patient Satisfaction for up to 6 Months With OnabotulinumtoxinA Treatment for Upper Facial Lines","volume":"48","author":"Cohen","year":"2022","journal-title":"Dermatol. Surg."},{"key":"ref_32","first-page":"11","article-title":"Servikal Distonilerin Botulinum Toksini ile Tedavisi","volume":"47","year":"2010","journal-title":"Arch. Neuropsychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Contarino, M.F., Van Den Dool, J., Balash, Y., Bhatia, K., Giladi, N., Koelman, J.H., Lokkegaard, A., Marti, M.J., Postma, M., and Relja, M. (2017). Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00035"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1007\/s00415-013-7220-8","article-title":"The effectiveness of physiotherapy for cervical dystonia: A systematic literature review","volume":"261","author":"Meirte","year":"2014","journal-title":"J. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e1287","DOI":"10.1016\/j.wneu.2020.11.153","article-title":"Cervical Myeloradiculopathy and Atlantoaxial Instability in Cervical Dystonia","volume":"146","author":"Neeraja","year":"2021","journal-title":"World Neurosurg."},{"key":"ref_36","unstructured":"(2024, May 28). St. Joseph\u2019s Health Care London Home Page. Available online: https:\/\/www.sjhc.london.on.ca\/media\/9742\/download."},{"key":"ref_37","unstructured":"(2024, May 28). BOTOX\u00ae Prescribing Information. Available online: https:\/\/www.botoxone.com\/adult-ndo\/dosing."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Erro, R., Picillo, M., Pellecchia, M.T., and Barone, P. (2023). Improving the Efficacy of Botulinum Toxin for Cervical Dystonia: A Scoping Review. Toxins, 15.","DOI":"10.3390\/toxins15060391"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1468-1331.2010.03042.x","article-title":"EFNS guidelines on diagnosis and treatment of primary dystonias","volume":"18","author":"Albanese","year":"2011","journal-title":"Eur. J. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Valls-Sole, J., and Defazio, G. (2016). Blepharospasm: Update on epidemiology, clinical aspects, and pathophysiology. Front. Neurol., 7.","DOI":"10.3389\/fneur.2016.00045"},{"key":"ref_41","first-page":"Cd006499","article-title":"Botulinum toxin for the treatment of strabismus","volume":"3","author":"Rowe","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/j.1469-8749.1998.tb15410.x","article-title":"What constitutes cerebral palsy?","volume":"40","author":"Badawi","year":"1998","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e32363","DOI":"10.1097\/MD.0000000000032363","article-title":"Treatment of pediatric spasticity, including children with cerebral palsy, with Botox [onabotulinumtoxinA]: Development, insights, and impact","volume":"102","author":"Gormley","year":"2023","journal-title":"Medicine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e2023093","DOI":"10.1590\/1984-0462\/2024\/42\/2023093","article-title":"The state of the art in therapeutic administration of botulinum toxin in children with cerebral palsy: An integrative review","volume":"42","author":"Dorf","year":"2024","journal-title":"Rev. Paul. Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s40272-019-00344-8","article-title":"Botulinum Toxin in the Management of Children with Cerebral Palsy","volume":"21","author":"Multani","year":"2019","journal-title":"Paediatr. Drugs"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Facciorusso, S., Spina, S., Picelli, A., Baricich, A., Francisco, G.E., Molteni, F., Wissel, J., and Santamato, A. (2024). The Role of Botulinum Toxin Type-A in Spasticity: Research Trends from a Bibliometric Analysis. Toxins, 16.","DOI":"10.3390\/toxins16040184"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Otero-Luis, I., Martinez-Rodrigo, A., Cavero-Redondo, I., Moreno-Herr\u00e1iz, N., Mart\u00ednez-Garc\u00eda, I., and Saz-Lara, A. (2024). Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030310"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ben-Pazi, H., Cohen, A., Kroyzer, N., Lotem-Ophir, R., Shvili, Y., Winter, G., Deutsch, L., and Pollak, Y. (2017). Clown-care reduces pain in children with cerebral palsy undergoing recurrent botulinum toxin injections\u2014A quasi-randomized controlled crossover study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175028"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11832-007-0075-8","article-title":"Long-term effect of repeated injections of botulinum toxin in children with cerebral palsy: A prospective study","volume":"2","author":"Domenievitz","year":"2008","journal-title":"J. Child. Orthop."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Baricich, A., Battaglia, M., Cuneo, D., Cosenza, L., Millevolte, M., Cosma, M., Filippetti, M., Dalise, S., Azzollini, V., and Chisari, C. (2023). Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1133390"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1212\/WNL.0000000000002560","article-title":"Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology","volume":"86","author":"Simpson","year":"2016","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s40265-018-1042-z","article-title":"Botulinum Toxin Type A for the Treatment of Lower Limb Spasticity after Stroke","volume":"79","author":"Santamato","year":"2019","journal-title":"Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Roncoroni, L.P., Weiss, D., Hieber, L., Sturm, J., B\u00f6rtlein, A., Mayr, I., Appy, M., K\u00fchnler, B., Buchthal, J., and Dippon, C. (2020). Health-Related Quality of Life Outcomes from Botulinum Toxin Treatment in Spasticity. Toxins, 12.","DOI":"10.3390\/toxins12050292"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Datta Gupta, A., Visvanathan, R., Cameron, I., Koblar, S.A., Howell, S., and Wilson, D. (2019). Efficacy of botulinum toxin in modifying spasticity to improve walking and quality of life in post-stroke lower limb spasticity\u2014A randomized double-blind placebo controlled study. BMC Neurol., 19.","DOI":"10.1186\/s12883-019-1325-3"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Baccouche, I., Bensmail, D., Leblong, E., Fraudet, B., Aymard, C., Quintaine, V., Pottier, S., Lansaman, T., Malot, C., and Gallien, P. (2022). Goal-Setting in Multiple Sclerosis-Related Spasticity Treated with Botulinum Toxin: The GASEPTOX Study. Toxins, 14.","DOI":"10.3390\/toxins14090582"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Novarella, F., Carotenuto, A., Cipullo, P., Iodice, R., Cassano, E., Spiezia, A.L., Capasso, N., Petracca, M., Falco, F., and Iacovazzo, C. (2022). Persistence with Botulinum Toxin Treatment for Spasticity Symptoms in Multiple Sclerosis. Toxins, 14.","DOI":"10.3390\/toxins14110774"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1056\/NEJMoa2304192","article-title":"Trial of Botulinum Toxin for Isolated or Essential Head Tremor","volume":"389","author":"Marques","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1212\/WNL.45.4.822","article-title":"Botulinum toxin treatment of essential head tremor","volume":"45","author":"Pahwa","year":"1995","journal-title":"Neurology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/ncpuro1124","article-title":"Drug Insight: Biological effects of botulinum toxin A in the lower urinary tract","volume":"5","author":"Chancellor","year":"2008","journal-title":"Nat. Clin. Pract. Urol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lin, Y.H., Chiang, B.J., and Liao, C.H. (2020). Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders. Toxins, 12.","DOI":"10.3390\/toxins12020129"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s42399-018-0005-8","article-title":"The management of urine storage dysfunction in the neurological patient","volume":"1","author":"Mehnert","year":"2019","journal-title":"SN Compr. Clin. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.eururo.2011.07.001","article-title":"Contemporary management of lower urinary tract disease with botulinum toxin A: A systematic review of botox [onabotulinumtoxinA] and dysport [abobotulinumtoxinA]","volume":"60","author":"Mangera","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.eururo.2011.12.056","article-title":"Botulinum toxin a versus placebo for refractory detrusor overactivity in women: A randomised blinded placebo-controlled trial of 240 women [the RELAX study]","volume":"62","author":"Tincello","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S0022-5347(01)66376-6","article-title":"Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: A prospective study in 24 spinal cord injury patients","volume":"155","author":"Schurch","year":"1996","journal-title":"J. Urol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.juro.2011.04.062","article-title":"Effects of 100 and 300 units of onabotulinum toxin A on lower urinary tract symptoms of benign prostatic hyperplasia: A phase II randomized clinical trial","volume":"186","author":"Crawford","year":"2011","journal-title":"J. Urol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.urology.2022.08.039","article-title":"Intra-Cavernosal Injection of Botulinum Toxin in the Treatment of Erectile Dysfunction: A Systematic Review and Meta-Analysis","volume":"170","author":"Mjaess","year":"2022","journal-title":"Urology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jsxm.2016.12.229","article-title":"Botox for erectile dysfunction","volume":"14","author":"Giuliano","year":"2017","journal-title":"J. Sex. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.jsxm.2019.06.002","article-title":"Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats","volume":"16","author":"Acar","year":"2019","journal-title":"J. Sex. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1007\/s00345-024-04899-1","article-title":"Is bulbospongiosus muscle botox injection safe and effective in treating lifelong premature ejaculation? Randomized controlled study","volume":"42","author":"Shaher","year":"2024","journal-title":"World J. Urol."},{"key":"ref_70","unstructured":"Rutstein, R.P., Cogen, M.S., Cotter, S.A., Daum, K., Mozlin, R., and Ryan, J. (2011). Optometric Clinical Practice Guideline Care of the Patient with Strabismus: Esotropia and Exotropia, American Optometric Association."},{"key":"ref_71","first-page":"16","article-title":"Correlation between Dermatology Life Quality Index and Minor test and differences in their levels over time in patients with axillary hyperhidrosis treated with botulinum toxin type A","volume":"19","author":"Skroza","year":"2011","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/j.1365-2133.2004.06334.x","article-title":"Psychosocial aspects of patients with focal hyperhidrosis. Marked reduction of social phobia, anxiety and depression and increased quality of life after treatment with botulinum toxin A","volume":"152","author":"Weber","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.jaad.2018.12.071","article-title":"The etiology, diagnosis, and management of hyperhidrosis: A comprehensive review: Etiology and clinical work-up","volume":"81","author":"Nawrocki","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e32764","DOI":"10.1097\/MD.0000000000032764","article-title":"Treatment of hyperhidrosis with Botox [onabotulinumtoxinA]: Development, insights, and impact","volume":"102","author":"Lowe","year":"2023","journal-title":"Medicine"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/exd.12650","article-title":"Novel TGM5 mutations in acral peeling skin syndrome","volume":"24","author":"Nellen","year":"2015","journal-title":"Exp. Dermatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"adv24305","DOI":"10.2340\/actadv.v104.24305","article-title":"Acral Peeling Skin Syndrome: Two Unusual Cases and the Therapeutic Potential of Botulinum Toxin","volume":"104","author":"Stjernbrandt","year":"2024","journal-title":"Acta Derm. Venereol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"567","DOI":"10.5114\/dr.2023.131389","article-title":"Acral peeling skin syndrome","volume":"110","author":"Gierach","year":"2023","journal-title":"Dermatol. Rev.\/Przegl\u0105d Dermatol."},{"key":"ref_78","first-page":"157","article-title":"The Role of Botulinum Toxin A in Treatment of Temporomandibular Joint Disorders: A Review","volume":"18","author":"Ataran","year":"2017","journal-title":"J. Dent."},{"key":"ref_79","unstructured":"Tintner, R., and Jankovic, J. (2002). Botulinum toxin type A in the management of oromandibular dystonia and bruxism. Scientific and Therapeutic Aspects of Botulinum Toxin, Lippincott Williams & Wilkins."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.tripleo.2004.11.019","article-title":"Treatment of severe temporomandibular joint clicking with botulinum toxin in the lateral pterygoid muscle in two cases of anterior disc displacement","volume":"100","author":"Bakke","year":"2005","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.bjoms.2004.01.010","article-title":"Reduction of a chronic bilateral temporomandibular joint dislocation with intermaxillary fixation and botulinum toxin A","volume":"42","author":"Aquilina","year":"2004","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0140-6736(10)62037-5","article-title":"National, regional, and global trends in body-mass index since 1980: Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9\u00b71 million participants","volume":"377","author":"Finucane","year":"2011","journal-title":"Lancet"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.dld.2008.02.040","article-title":"Effects of intramural administration of Botulinum Toxin A on gastric emptying and eating capacity in obese patients","volume":"40","author":"Foschi","year":"2008","journal-title":"Dig. Liver Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.gie.2015.08.029","article-title":"Reviewing the reviewers: Critical appraisal of \u201cEffect of intragastric injection of botulinum toxin A for the treatment of obesity: A meta-analysis and meta-regression\u201d","volume":"83","author":"Bustamante","year":"2016","journal-title":"Gastrointest Endosc."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.regpep.2004.08.007","article-title":"Ghrelin: A gastric peptide that regulates food intake and energy homeostasis","volume":"126","author":"Ueno","year":"2005","journal-title":"Regul. Pept."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/j.1467-789X.2011.00964.x","article-title":"Prevalence of general and abdominal obesity in the adult population of Spain, 2008\u20132010: The ENRICA study","volume":"13","author":"Graciani","year":"2012","journal-title":"Obes. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.clnu.2020.10.008","article-title":"Endoscopic intragastric injection of botulinum toxin A in obese patients on bariatric surgery waiting lists: A randomised double-blind study [IntraTox study]","volume":"40","author":"Tapia","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s11883-002-0049-8","article-title":"Obesity and cardiovascular disease","volume":"4","author":"Poirier","year":"2002","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5946\/ce.2017.007","article-title":"Recent Trends in Endoscopic Bariatric Therapies","volume":"50","author":"Choi","year":"2017","journal-title":"Clin. Endosc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1055\/s-2004-830901","article-title":"Botulism: Update and review","volume":"24","author":"Cherington","year":"2004","journal-title":"Semin. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/head.12999","article-title":"Chronic Migraine: An Update on Physiology, Imaging, and the Mechanism of Action of Two Available Pharmacologic Therapies","volume":"57","author":"Aurora","year":"2017","journal-title":"Headache"},{"key":"ref_92","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. Psychiatry"},{"key":"ref_93","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_94","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s10194-017-0773-7","article-title":"Onabotulinumtoxin A for the management of chronic migraine in current clinical practice: Results of a survey of sixty-three Italian headache centers","volume":"18","author":"Tassorelli","year":"2017","journal-title":"J. Headache Pain"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s10194-024-01721-6","article-title":"Real-world effectiveness of Anti-CGRP monoclonal antibodies compared to OnabotulinumtoxinA [RAMO] in chronic migraine: A retrospective, observational, multicenter, cohort study","volume":"25","author":"Grazzi","year":"2024","journal-title":"J. Headache Pain"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Grazzi, L., Montisano, D.A., Rizzoli, P., Guastafierro, E., Marcassoli, A., Fornari, A., and Raggi, A. (2023). A Single-Group Study on the Effect of OnabotulinumtoxinA in Patients with Chronic Migraine Associated with Medication Overuse Headache: Pain Catastrophizing Plays a Role. Toxins, 15.","DOI":"10.3390\/toxins15020086"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s10194-016-0702-1","article-title":"Real-life data in 115 chronic migraine patients treated with Onabotulinumtoxin A during more than one year","volume":"17","author":"Rojo","year":"2016","journal-title":"J. Headache Pain"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Onan, D., Bentivegna, E., and Martelletti, P. (2023). OnabotulinumtoxinA Treatment in Chronic Migraine: Investigation of Its Effects on Disability, Headache and Neck Pain Intensity. Toxins, 15.","DOI":"10.3390\/toxins15120685"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Onan, D., Ar\u0131kan, H., and Martelletti, P. (2023). The Effect of OnabotulinumtoxinA on Headache Intensity and Number of Monthly Headache Days in Individuals with Chronic Migraine with Different Levels of Neck Disability. Toxins, 15.","DOI":"10.3390\/toxins15120685"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s10194-023-01622-0","article-title":"Real-world effectiveness, satisfaction, and optimization of ubrogepant for the acute treatment of migraine in combination with onabotulinumtoxinA: Results from the COURAGE Study","volume":"24","author":"Hutchinson","year":"2023","journal-title":"J. Headache Pain."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s10194-023-01696-w","article-title":"Clinical effectiveness of pharmacological interventions for managing chronic migraine in adults: A systematic review and network meta-analysis","volume":"24","author":"Naghdi","year":"2023","journal-title":"J. Headache Pain"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s00253-021-11741-w","article-title":"Botulinum toxin in cancer therapy\u2014Current perspectives and limitations","volume":"106","author":"Grenda","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.3390\/toxins7083127","article-title":"Botulinum Toxin for Neuropathic Pain: A Review of the Literature","volume":"7","author":"Oh","year":"2015","journal-title":"Toxins"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Park, J., and Park, H.J. (2017). Botulinum Toxin for the Treatment of Neuropathic Pain. Toxins, 9.","DOI":"10.3390\/toxins9090260"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Matak, I., B\u00f6lcskei, K., Bach-Rojecky, L., and Helyes, Z. (2019). Mechanisms of Botulinum Toxin Type A Action on Pain. Toxins, 11.","DOI":"10.3390\/toxins11080459"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/hed.10340","article-title":"Botulinum toxin type A for the treatment of chronic neck pain after neck dissection","volume":"26","author":"Vasan","year":"2004","journal-title":"Head Neck"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Mittal, S.O., and Jabbari, B. (2020). Botulinum Neurotoxins and Cancer-A Review of the Literature. Toxins, 12.","DOI":"10.3390\/toxins12010032"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.3390\/toxins5051010","article-title":"Sialorrhea: Anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins","volume":"5","author":"Lakraj","year":"2013","journal-title":"Toxins"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.tox.2015.07.003","article-title":"Botulinum neurotoxin type A: Actions beyond SNAP-25?","volume":"335","author":"Matak","year":"2015","journal-title":"Toxicology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/pros.20958","article-title":"Botulinum toxin type A inhibits the growth of LNCaP human prostate cancer cells in vitro and in vivo","volume":"69","author":"Karsenty","year":"2009","journal-title":"Prostate"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"50","DOI":"10.4014\/jmb.1107.07018","article-title":"Cells transformed by PLC-gamma 1 overexpression are highly sensitive to clostridium difficile toxin A-induced apoptosis and mitotic inhibition","volume":"22","author":"Nam","year":"2012","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5301\/RU.2012.9254","article-title":"Botulinum toxin type-A toxin activity on prostate cancer cell lines","volume":"79","author":"Proietti","year":"2012","journal-title":"Urologia"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"891","DOI":"10.7314\/APJCP.2013.14.2.891","article-title":"Effect of botulinum toxin A on proliferation and apoptosis in the T47D breast cancer cell line","volume":"14","author":"Bandala","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_114","first-page":"e2","article-title":"The Use of Botulinum Toxin A in the Management of Trigeminal Neuralgia: A Systematic Literature Review","volume":"11","author":"Rubis","year":"2020","journal-title":"J. Oral Maxillofac. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1177\/0333102412459577","article-title":"Botulinum toxin for trigeminal neuralgia\u2014Do we have the evidence?","volume":"32","author":"Zakrzewska","year":"2012","journal-title":"Cephalalgia"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e8133","DOI":"10.1097\/MD.0000000000008133","article-title":"Botulinum toxin in the treatment of trigeminal neuralgia: 6-Month follow-up","volume":"96","author":"Duman","year":"2017","journal-title":"Medicine"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"543","DOI":"10.23736\/S0390-5616.20.05125-5","article-title":"A reappraisal on botulinum toxin-a in trigeminal neuralgia","volume":"65","author":"Spina","year":"2021","journal-title":"J. Neurosurg. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuropharm.2018.06.016","article-title":"A SNAP-25 cleaving chimera of botulinum neurotoxin \/A and \/E prevents TNF\u03b1-induced elevation of the activities of native TRP channels on early postnatal rat dorsal root ganglion neurons","volume":"138","author":"Nugent","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_119","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_120","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1055\/s-0035-1571213","article-title":"Botulinum toxin: Preparations for clinical use, immunogenicity, side effects, and safety profile","volume":"36","author":"Dashtipour","year":"2016","journal-title":"Semin. Neurol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.pain.2011.06.017","article-title":"A new definition of neuropathic pain","volume":"152","author":"Jensen","year":"2011","journal-title":"Pain"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/ana.21427","article-title":"Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain","volume":"64","author":"Ranoux","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1212\/01.wnl.0000345968.05959.cf","article-title":"Botulinum toxin for diabetic neuropathic pain: A randomized double-blind crossover trial","volume":"72","author":"Yuan","year":"2009","journal-title":"Neurology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1111\/j.1526-4637.2010.01003.x","article-title":"Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia","volume":"11","author":"Xiao","year":"2010","journal-title":"Pain Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1007\/s42399-020-00286-0","article-title":"Trigger Point Injections: A Systematic, Narrative Review of the Current Literature","volume":"2","author":"Walker","year":"2020","journal-title":"SN Compr. Clin. Med."},{"key":"ref_126","unstructured":"Travell, J.G., and Simons, D.G. (1992). Myofascial Pain and Dysfunction: The Trigger Point Manual, Lippincott Williams & Wilkins."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.pain.2006.05.001","article-title":"Dysport myofascial pain study group. Efficacy and safety of a single botulinum type A toxin complex treatment (Dysport) for the relief of upper back myofascial pain syndrome: Results from a randomized double-blind placebo-controlled multicentre study","volume":"125","author":"Heinze","year":"2006","journal-title":"Pain"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/00000542-200508000-00021","article-title":"Evidence against trigger point injection technique for the treatment of cervicothoracic myofascial pain with botulinum toxin type A","volume":"103","author":"Ferrante","year":"2005","journal-title":"Anesthesiology"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.pain.2005.08.012","article-title":"Botulinum toxin A versus bupivacaine trigger point injections for the treatment of myofascial pain syndrome: A randomised double blind crossover study","volume":"118","author":"Graboski","year":"2005","journal-title":"Pain"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"821e","DOI":"10.1097\/PRS.0000000000002625","article-title":"Effect of Botulinum Toxin Type A on TGF-\u03b2\/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation","volume":"138","author":"Kim","year":"2016","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1016\/j.jaad.2020.04.082","article-title":"The effect of intradermal botulinum toxin on androgenetic alopecia and its possible mechanism","volume":"83","author":"Shon","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e13696","DOI":"10.1111\/srt.13696","article-title":"Efficacy and safety of botulinum toxin A in the treatment of female pattern hair loss","volume":"30","author":"Hu","year":"2024","journal-title":"Skin Res. Technol."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Yu, S., Zhao, J., Feng, X., Zhang, M., and Zhao, Z. (2020). Effectiveness and Safety of Botulinum Toxin Type A in the Treatment of Androgenetic Alopecia. BioMed Res. 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