{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T01:45:44Z","timestamp":1783734344685,"version":"3.55.0"},"reference-count":106,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100005989","name":"Ministry of Education, Science and Sport","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005989","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Croatian National Science Foundation"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicon"],"published-print":{"date-parts":[[2020,5]]},"DOI":"10.1016\/j.toxicon.2020.02.008","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T13:38:25Z","timestamp":1581428305000},"page":"1-7","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["New analgesic: Focus on botulinum toxin"],"prefix":"10.1016","volume":"179","author":[{"given":"Zdravko","family":"Lackovi\u0107","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxicon.2020.02.008_bib1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/j.1476-5381.2011.01781.x","article-title":"Analgesic conotoxins: block and G protein-coupled receptor modulation of N-type (Ca(V) 2.2) calcium channels","volume":"166","author":"Adams","year":"2012","journal-title":"Br. J. Pharmacol."},{"issue":"6Suppl. l","key":"10.1016\/j.toxicon.2020.02.008_bib2","doi-asserted-by":"crossref","first-page":"S177","DOI":"10.1097\/00002508-200211001-00010","article-title":"A focused review on the use of botulinum toxins for neuropathic pain","volume":"18","author":"Argoff","year":"2002","journal-title":"Clin. J. Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib3","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1001\/jama.285.8.1059","article-title":"Botulinum toxin as a biological weapon: medical and public health management","volume":"285","author":"Arnon","year":"2001","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.toxicon.2020.02.008_bib4","series-title":"Information for Healthcare Professionals: OnabotulinumtoxinA 383 (Marketed as Botox\/Botox Cosmetic), AbobotulinumtoxinA (Marketed as Dysport. And RimabotulinumtoxinB (Marketed as Myobloc)","author":"FDA","year":"2009"},{"key":"10.1016\/j.toxicon.2020.02.008_bib113","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1472-8206.2008.00615.x","article-title":"Lack of anti-inflammatory effect of botulinum toxin type A in experimental models of inflammation","volume":"22","author":"Bach-Rojecky","year":"2008","journal-title":"Fundam. Clin. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib5","first-page":"201","article-title":"Antinociceptive effect of botulinum toxin type a in rat model of carrageenan and capsaicin induced pain","volume":"46","author":"Bach-Rojecky","year":"2005","journal-title":"Croat. Med. J."},{"key":"10.1016\/j.toxicon.2020.02.008_bib6","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.pbb.2009.08.012","article-title":"Central origin of the antinociceptive action of botulinum toxin type A","volume":"94","author":"Bach-Rojecky","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.toxicon.2020.02.008_bib7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00702-004-0265-1","article-title":"Botulinum toxin type A in experimental neuropathic pain","volume":"112","author":"Bach-Rojecky","year":"2005","journal-title":"J. Neural. Transm."},{"key":"10.1016\/j.toxicon.2020.02.008_bib8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejphar.2010.01.020","article-title":"Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection","volume":"633","author":"Bach-Rojecky","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib9","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1001\/archinte.163.20.2433","article-title":"Depression and pain comorbidity: a literature review","volume":"163","author":"Bair","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"10.1016\/j.toxicon.2020.02.008_bib10","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1002\/art.38772","article-title":"Differential regulatory role of pituitary adenylate cyclase-activating polypeptide in the serum-transfer arthritis model","volume":"66","author":"Botz","year":"2014","journal-title":"Arthritis Rheum."},{"key":"10.1016\/j.toxicon.2020.02.008_bib12","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3390\/toxins10050175","article-title":"Exploiting botulinum neurotoxins for the study of brain physiology and pathology","volume":"10","author":"Caleo","year":"2018","journal-title":"Toxins"},{"key":"10.1016\/j.toxicon.2020.02.008_bib13","doi-asserted-by":"crossref","first-page":"10329","DOI":"10.1523\/JNEUROSCI.0294-18.2018","article-title":"Transynaptic action of botulinum neurotoxin type A at central cholinergic boutons","volume":"38","author":"Caleo","year":"2018","journal-title":"J. Neurosci."},{"key":"10.1016\/j.toxicon.2020.02.008_bib14","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1111\/j.1526-4637.2011.01135.x","article-title":"Human response to unintended intrathecal injection of botulinum toxin","volume":"2","author":"Carroll","year":"2011","journal-title":"Pain Med."},{"key":"10.1016\/j.toxicon.2020.02.008_bib15","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.eururo.2008.05.007","article-title":"Intravesical botulinum toxin A administration inhibits COX-2 and EP4 expression and suppresses bladder hyperactivity in cyclophosphamide-induced cystitis in rats","volume":"56","author":"Chuan","year":"2009","journal-title":"Eur. Urol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib16","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1097\/01.ju.0000137844.77524.97","article-title":"Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats","volume":"172","author":"Chuang","year":"2004","journal-title":"J. Urol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib17","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.juro.2007.07.120","article-title":"Intraprostatic botulinum toxin a injection inhibits cyclooxygenase-2 expression and suppresses prostatic pain on capsaicin induced prostatitis model in rat","volume":"180","author":"Chuang","year":"2008","journal-title":"J. Urol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib18","author":"Citizen"},{"issue":"10","key":"10.1016\/j.toxicon.2020.02.008_bib19","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1002\/ejp.513","article-title":"Intrathecal administration of botulinum toxin type A improves urinary bladder function and reduces pain in rats with cystitis","volume":"18","author":"Coelho","year":"2014","journal-title":"Eur. J. Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib20","first-page":"199","article-title":"No evidence of real progress in treatment of acute pain, 1993-2012: scientometric analysis","volume":"7","author":"Correll","year":"2014","journal-title":"J. Pain Res."},{"key":"10.1016\/j.toxicon.2020.02.008_bib21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.jaad.2005.06.011","article-title":"Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases","volume":"53","author":"Cot\u00e9","year":"2005","journal-title":"J. Am. Acad. Dermatol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib22","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":"10.1016\/j.toxicon.2020.02.008_bib23","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":"10.1016\/j.toxicon.2020.02.008_bib24","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ejphar.2014.10.038","article-title":"Antinociceptive effect of botulinum toxin type A on experimental abdominal pain","volume":"745","author":"Drinovac","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib25","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00702-013-1150-6","article-title":"Association of antinociceptive action of botulinum toxin type A with GABA-A receptor","volume":"121","author":"Drinovac","year":"2014","journal-title":"J. Neural. Transm."},{"key":"10.1016\/j.toxicon.2020.02.008_bib26","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neuropharm.2013.02.011","article-title":"Involvement of \u03bc-opioid receptors in antinociceptive action of botulinum toxin type A","volume":"70","author":"Drinovac Vlah","year":"2013","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.toxicon.2020.02.008_bib27","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s00702-016-1605-7","article-title":"Antinociceptive action 355 of botulinum toxin type A in carrageenan-induced mirror pain","volume":"123","author":"Drinovac Vlah","year":"2016","journal-title":"J. Neural. Transm."},{"key":"10.1016\/j.toxicon.2020.02.008_bib28","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/ejp.1146","article-title":"Role of central versus peripheral opioid system in antinociceptive and anti-inflammatory effect of botulinum toxin type A in trigeminal region","volume":"3","author":"Drinovac Vlah","year":"2018","journal-title":"Eur. J. Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1527-3458.2007.00002.x","article-title":"MD-354: what is it good for?","volume":"13","author":"Dukat","year":"1997","journal-title":"CNS Drug Rev."},{"key":"10.1016\/j.toxicon.2020.02.008_bib30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s10194-018-0852-4","article-title":"PACAP and its role in primary headaches","volume":"19","author":"Edvinsson","year":"2018","journal-title":"J. Headache Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib31","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.toxicon.2017.05.001","article-title":"Botulinum toxin type A reduces TRPV1 expression in the dorsal root ganglion in rats with adjuvant-arthritis pain","volume":"133","author":"Fan","year":"2017","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2020.02.008_bib32","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejphar.2009.06.047","article-title":"Different antinociceptive effects of botulinum toxin type A in inflammatory and peripheral polyneuropathic rat models","volume":"617","author":"Favre-Guilmard","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib33","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/ejp.995","article-title":"Bilateral analgesic effects of abobotulinumtoxinA (Dysport\u00ae ) following unilateral administration in the rat","volume":"21","author":"Favre-Guilmard","year":"2017","journal-title":"Eur. J. Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib34","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.3389\/fimmu.2019.01027","article-title":"Cannabinoid receptor 2 agonist JWH-015 inhibits interleukin-1\u03b2-induced inflammation in rheumatoid arthritis synovial fibroblasts and in adjuvant induced arthritis rat via glucocorticoid receptor","volume":"10","author":"Fechtner","year":"2019","journal-title":"Front. Immunol."},{"issue":"1","key":"10.1016\/j.toxicon.2020.02.008_bib35","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1472-8206.2009.00767.x","article-title":"Lasting reduction of postsurgical hyperalgesia after single injection of botulinum toxin type A in rat","volume":"24","author":"Filipovi\u0107","year":"2010","journal-title":"Fundam. Clin. Pharmacol."},{"issue":"1","key":"10.1016\/j.toxicon.2020.02.008_bib36","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029803","article-title":"Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy","volume":"7","author":"Filipovi\u0107","year":"2012","journal-title":"PloS One"},{"issue":"5","key":"10.1016\/j.toxicon.2020.02.008_bib37","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00702-013-1144-4","article-title":"Dural neurogenic inflammation induced by neuropathic pain is specific to cranial region","volume":"121","author":"Filipovi\u0107","year":"2014","journal-title":"J. Neural. Transm."},{"issue":"2","key":"10.1016\/j.toxicon.2020.02.008_bib38","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/00002508-199706000-00006","article-title":"Chronic pain-associated depression: antecedent or consequence of chronic pain? A review","volume":"13","author":"Fishbain","year":"1977","journal-title":"Clin. J. Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib39","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":"10.1016\/j.toxicon.2020.02.008_bib40","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1517\/14728214.2014.915025","article-title":"Emerging drugs for neuropathic pain","volume":"19","author":"Gilron","year":"2014","journal-title":"Expet Opin. Emerg. Drugs"},{"key":"10.1016\/j.toxicon.2020.02.008_bib41","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/JCP.0000000000000995","article-title":"Assessment of the abuse potential of cebranopadol in nondependent recreational opioid users: a phase 1 randomized controlled study","volume":"1","author":"G\u00f6hler","year":"2019","journal-title":"J. Clin. Psychopharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib42","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.pain.2011.09.008","article-title":"Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker","volume":"153","author":"Goldberg","year":"2012","journal-title":"Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/00004872-200203000-00024","article-title":"Changes in pain perception during treatment with angiotensin converting enzyme-inhibitors and angiotensin II type 1 receptor blockade","volume":"20","author":"Guasti","year":"2002","journal-title":"J. Hypertens."},{"key":"10.1016\/j.toxicon.2020.02.008_bib44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.pain.2010.06.022","article-title":"NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation","volume":"15","author":"Gustin","year":"2010","journal-title":"Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib45","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/BF00500611","article-title":"125I-labeled neurotoxin from Clostridium botulinum A: preparation, binding to synaptosomes and ascent to the spinal cord","volume":"281","author":"Habermann","year":"1974","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib46","doi-asserted-by":"crossref","first-page":"680","DOI":"10.3390\/md11030680","article-title":"Omega-conotoxins as experimental tools and therapeutics in pain management","volume":"1 1","author":"Hannon","year":"2013","journal-title":"Mar. Drugs"},{"key":"10.1016\/j.toxicon.2020.02.008_bib47","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1001\/jama.2012.4526","article-title":"Epidemic of prescription opiate abuse and neonatal abstinence","volume":"307","author":"Hayes","year":"2012","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.toxicon.2020.02.008_bib48","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12917-017-0990-y","article-title":"The effect of intraarticular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint","volume":"13","author":"Heikkil\u00e4","year":"2017","journal-title":"BMC Vet. Res."},{"issue":"1","key":"10.1016\/j.toxicon.2020.02.008_bib49","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0191043","article-title":"Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: a placebo controlled, blinded, randomized trial","volume":"13","author":"Heikkil\u00e4","year":"2018","journal-title":"PloS One"},{"key":"10.1016\/j.toxicon.2020.02.008_bib50","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.neuroscience.2017.06.004","article-title":"Antinociceptive effect of botulinum toxin A involves alterations in AMPA receptor expression and glutamate release in spinal dorsal horn neurons","volume":"357","author":"Hong","year":"2017","journal-title":"Neuroscience"},{"key":"10.1016\/j.toxicon.2020.02.008_bib114","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1111\/j.1526-4637.2011.01245.x","article-title":"Treatment of refractory pain with botulinum toxins--an evidence-based review","volume":"12","author":"Jabbari","year":"2011","journal-title":"Pain Med."},{"key":"10.1016\/j.toxicon.2020.02.008_bib51","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/jor.23412","article-title":"Nociception contributes to the formation of myogenic contracture in the early phase of adjuvant-induced arthritis in a rat knee","volume":"35","author":"Kaneguchi","year":"2017","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.toxicon.2020.02.008_bib52","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1213\/ANE.0b013e3181cde882","article-title":"The development of new analgesics over the past 50 years: a lack of real breakthrough drugs","volume":"110","author":"Kissin","year":"2010","journal-title":"Anesth. Analg."},{"issue":"4","key":"10.1016\/j.toxicon.2020.02.008_bib53","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.neuroscience.2009.01.066","article-title":"Botulinum toxin type a (150 kDa) decreases exaggerated neurotransmitter release from trigeminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction","volume":"159","author":"Kitamura","year":"2009","journal-title":"Neuroscience"},{"key":"10.1016\/j.toxicon.2020.02.008_bib54","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1365-2842.2011.02236.x","article-title":"Intradermal injection of Botulinum toxin type A alleviates infraorbital nerve constriction-induced thermal hyperalgesia in an operant assay","volume":"39","author":"Kumada","year":"2012","journal-title":"J. Oral Rehabil."},{"key":"10.1016\/j.toxicon.2020.02.008_bib55","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s00702-009-0285-y","article-title":"Single intracerebroventricular injection of botulinum toxin type A produces slow onset and long-term memory impairment in rats","volume":"116","author":"Lackovi\u0107","year":"2009","journal-title":"J. Neural. Transm."},{"key":"10.1016\/j.toxicon.2020.02.008_bib56","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/bph.13366","article-title":"Activity of botulinum toxin type A in cranial dura: implications for treatment of migraine and other headaches","volume":"173","author":"Lackovi\u0107","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib57","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3928\/02793695-20170119-03","article-title":"The opioid epidemic: what does it mean for nurses?","volume":"1","author":"Leahym","year":"2017","journal-title":"J. Psychosoc. Nurs. Ment. Health Serv."},{"key":"10.1016\/j.toxicon.2020.02.008_bib58","article-title":"Cannabinoid CB2 agonist AM1710 differentially suppresses distinct pathological pain states and attenuates morphine tolerance and withdrawal","volume":"116670","author":"Li","year":"2019","journal-title":"Life Sci."},{"key":"10.1016\/j.toxicon.2020.02.008_bib59","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/01.fbp.0000129746.14753.1e","article-title":"Central injection of botulinum neurotoxins: behavioural effects in mice","volume":"15","author":"Luvisetto","year":"2004","journal-title":"Behav. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib63","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.neuroscience.2010.08.067","article-title":"Botulinum neurotoxin type A counteracts neuropathic pain and facilitates functional recovery after peripheral nerve injury in animal models","volume":"171","author":"Marinelli","year":"2010","journal-title":"Neuroscience"},{"key":"10.1016\/j.toxicon.2020.02.008_bib64","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/bph.14846","article-title":"Evidence for central antispastic effect of botulinum toxin type A","volume":"177","author":"Matak","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib66","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"},{"issue":"2","key":"10.1016\/j.toxicon.2020.02.008_bib67","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.neuint.2012.05.001","article-title":"Botulinum toxin's axonal transport from periphery to the spinal cord","volume":"61","author":"Matak","year":"2012","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.toxicon.2020.02.008_bib68","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neuroscience.2017.06.040","article-title":"Involvement of substance P in the antinociceptive effect of botulinum toxin type A: evidence from knockout mice","volume":"358","author":"Matak","year":"2017","journal-title":"Neuroscience"},{"issue":"1","key":"10.1016\/j.toxicon.2020.02.008_bib70","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.pain.2007.11.006","article-title":"Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain","volume":"138","author":"Medhurst","year":"2008","journal-title":"Pain"},{"key":"10.1016\/j.toxicon.2020.02.008_bib71","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.neuroscience.2010.11.040","article-title":"The effect of botulinum neurotoxin A on sciatic nerve injury-induced neuroimmunological changes in rat dorsal root ganglia and spinal cord","volume":"175","author":"Mika","year":"2011","journal-title":"Neuroscience"},{"key":"10.1016\/j.toxicon.2020.02.008_bib72","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.toxicon.2017.02.010","article-title":"Botulinum toxin type A reduces inflammatory hypernociception induced by arthritis in the temporomadibular joint of rats","volume":"129","author":"Mu\u00f1oz-Lora","year":"2017","journal-title":"Toxicon"},{"issue":"1","key":"10.1016\/j.toxicon.2020.02.008_bib74","doi-asserted-by":"crossref","first-page":"7468","DOI":"10.1038\/s41598-019-43858-4","article-title":"CB2 receptor deletion on myeloid cells enhanced mechanical allodynia in a mouse model of neuropathic pain","volume":"9","author":"Nent","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.toxicon.2020.02.008_bib75","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1292\/jvms.18-0506","article-title":"Intra-articular botulinum toxin A (BoNT\/A) for pain management in dogs with osteoarthritis secondary to hip dysplasia: a randomized controlled clinical trial","volume":"81","author":"Nic\u00e1cio","year":"2019","journal-title":"J. Vet. Med. Sci."},{"issue":"2","key":"10.1016\/j.toxicon.2020.02.008_bib76","doi-asserted-by":"crossref","first-page":"95","DOI":"10.4103\/0974-2077.44169","article-title":"Botulinum toxin deaths: what is the fact?","volume":"1","author":"Omprakash","year":"2008","journal-title":"J. Cutan. Aesthetic Surg."},{"issue":"5","key":"10.1016\/j.toxicon.2020.02.008_bib77","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/BF03022619","article-title":"The effects of botulinum toxin A on mechanical and cold allodynia in a rat model of neuropathic pain","volume":"53","author":"Park","year":"2006","journal-title":"Can. J. Anaesth."},{"key":"10.1016\/j.toxicon.2020.02.008_bib78","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jaad.2008.12.042","article-title":"Serious issues relating to the clinical use of unlicensed botulinum toxinproducts","volume":"61","author":"Pickett","year":"2009","journal-title":"J. Am. Acad. Dermatol."},{"issue":"2","key":"10.1016\/j.toxicon.2020.02.008_bib79","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1124\/pr.116.012658","article-title":"Botulinum neurotoxins: biology, pharmacology, and toxicology","volume":"69","author":"Pirazzini","year":"2017","journal-title":"Pharmacol. Rev."},{"issue":"44","key":"10.1016\/j.toxicon.2020.02.008_bib80","doi-asserted-by":"crossref","first-page":"15650","DOI":"10.1523\/JNEUROSCI.2618-11.2011","article-title":"Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT\/A)","volume":"31","author":"Restani","year":"2011","journal-title":"J. Neurosci."},{"issue":"12","key":"10.1016\/j.toxicon.2020.02.008_bib81","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003087","article-title":"Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons","volume":"8","author":"Restani","year":"2012","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.toxicon.2020.02.008_bib82","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.toxicon.2017.11.004","article-title":"Neosaxitoxin, a Paralytic Shellfish Poison toxin, effectively manages bucked shins pain, as a local long-acting pain blocker in an equine model","volume":"141","author":"Riquelme","year":"2017","journal-title":"Toxicon"},{"issue":"32","key":"10.1016\/j.toxicon.2020.02.008_bib83","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.2174\/0929867324666170529072554","article-title":"The orexinergic (hypocretin) system and nociception: an update to supraspinal mechanisms","volume":"25","author":"Roohbakhsh","year":"2018","journal-title":"Curr. Med. Chem."},{"issue":"8","key":"10.1016\/j.toxicon.2020.02.008_bib84","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":"10.1016\/j.toxicon.2020.02.008_bib85","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.toxicon.2018.01.017","article-title":"Botulinum toxin treatment of pain syndromes -an evidence based review","volume":"147","author":"Safarpour","year":"2018","journal-title":"Toxicon"},{"issue":"8","key":"10.1016\/j.toxicon.2020.02.008_bib86","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.2174\/1570159X16666180510151241","article-title":"Experimental drugs for neuropathic pain","volume":"16","author":"Salat","year":"2018","journal-title":"Curr. Neuropharmacol."},{"issue":"4","key":"10.1016\/j.toxicon.2020.02.008_bib87","first-page":"443","article-title":"Pharmacokinetics of a novel, transdermal fentanyl solution in Rhesus Macaques (Macaca mulatta)","volume":"56","author":"Salyards","year":"2017","journal-title":"J Am Assoc Lab Anim Sci"},{"issue":"3","key":"10.1016\/j.toxicon.2020.02.008_bib88","doi-asserted-by":"crossref","first-page":"E193","DOI":"10.36076\/ppj.2018.3.E193","article-title":"Cebranopadol: a novel, first-in-class, strong analgesic: results from a randomized phase IIa clinical trial in postoperative acute pain","volume":"21","author":"Scholz","year":"2018","journal-title":"Pain Physician"},{"issue":"3","key":"10.1016\/j.toxicon.2020.02.008_bib89","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":"10.1016\/j.toxicon.2020.02.008_bib90","doi-asserted-by":"crossref","first-page":"v12","DOI":"10.1016\/j.toxicon.2012.12.011","article-title":"Antinociceptive effects of A1 and A2 type botulinum toxins on carrageenan-induced hyperalgesia in rat","volume":"64","author":"Shin","year":"2013","journal-title":"Toxicon"},{"issue":"1","key":"10.1016\/j.toxicon.2020.02.008_bib91","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1067\/maj.2002.121958","article-title":"Clinical results of botulinum toxin type a treatment of migraine headache","volume":"22","author":"Silberstein","year":"2002","journal-title":"Aesthetic Surg. J."},{"key":"10.1016\/j.toxicon.2020.02.008_bib92","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.resmic.2014.09.007","article-title":"Historical and current perspectives on Clostridium botulinum diversity","volume":"166","author":"Smith","year":"2015","journal-title":"Res. Microbiol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib93","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.toxicon.2017.10.008","article-title":"The travel diaries of tetanus and botulinum neurotoxins","volume":"147","author":"Surana","year":"2018","journal-title":"Toxicon"},{"issue":"2","key":"10.1016\/j.toxicon.2020.02.008_bib94","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jphs.2018.11.011","article-title":"The novel small-molecule antagonist of PAC1 receptor attenuates formalin-induced inflammatory pain behaviors in mice","volume":"139","author":"Takasaki","year":"2019","journal-title":"J Pharmacol 573 Sci."},{"issue":"1\u20133","key":"10.1016\/j.toxicon.2020.02.008_bib95","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.ejphar.2013.07.029","article-title":"Mechanisms involved in abdominal nociception induced by either TRPV1 or TRPA1 stimulation of rat peritoneum","volume":"714","author":"Trevisan","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib96","doi-asserted-by":"crossref","first-page":"16554","DOI":"10.1073\/pnas.1008302107","article-title":"Targeting botulinum neurotoxin persistence by the ubiquitin-proteasome system","volume":"107","author":"Tsai","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"8501","key":"10.1016\/j.toxicon.2020.02.008_bib97","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0140-6736(86)92070-2","article-title":"Double-blind study of botulinum toxin in spasmodic torticollis","volume":"2","author":"Tsui","year":"1986","journal-title":"Lancet"},{"issue":"3","key":"10.1016\/j.toxicon.2020.02.008_bib98","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.bbi.2012.01.002","article-title":"Botulinum neurotoxin A enhances the analgesic effects on inflammatory pain and antagonizes tolerance induced by morphine in mice","volume":"26","author":"Vacca","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.toxicon.2020.02.008_bib99","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bbi.2013.01.088","article-title":"Botulinum toxin A increases analgesic effects of morphine, counters development of morphine tolerance and modulates glia activation and \u03bc opioid receptor expression in neuropathic mice","volume":"32","author":"Vacca","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.toxicon.2020.02.008_bib100","first-page":"155","article-title":"Evaluation of protective effects of non-selective cannabinoid receptor agonist WIN 55,212-2 against the nitroglycerine-induced acute and chronic animal models of migraine: a mechanistic study","volume":"2","author":"Vosough","year":"2019","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib101","first-page":"551","article-title":"Randomized, double-blind, placebo-controlled, crossover study of the T-type CalciumChannel blocker ABT-639 in an intradermal capsaicin experimental pain model in healthy adults","volume":"3","author":"Wallace","year":"2016","journal-title":"Pain Med."},{"key":"10.1016\/j.toxicon.2020.02.008_bib102","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.toxicon.2016.11.009","article-title":"Intra-articular injection of Botulinum toxin A reduces neurogenic inflammation in CFA-induced arthritic rat model","volume":"126","author":"Wang","year":"2017","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2020.02.008_bib103","doi-asserted-by":"crossref","first-page":"1657498","DOI":"10.1155\/2019\/1657498","article-title":"Bibliometric study of the comorbidity of pain and depression research","volume":"2019","author":"Wang","year":"2019","journal-title":"Neural Plast."},{"key":"10.1016\/j.toxicon.2020.02.008_bib104","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/BF00498587","article-title":"125I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection","volume":"292","author":"Wiegand","year":"1976","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"10.1016\/j.toxicon.2020.02.008_bib105","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/pme.12017","article-title":"Botulinum toxin type A reduces hyperalgesia and TRPV1 expression in rats with neuropathic pain","volume":"14","author":"Xia","year":"2013","journal-title":"Pain Med."},{"key":"10.1016\/j.toxicon.2020.02.008_bib106","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1111\/j.1526-4637.2011.01182.x","article-title":"Botulinum toxin decreases hyperalgesia and inhibits P2X3 receptor over-expression in sensory neurons induced by ventral root transection in rats","volume":"12","author":"Xiao","year":"2011","journal-title":"Pain Med."},{"key":"10.1016\/j.toxicon.2020.02.008_bib107","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/j.1526-4637.2011.01164.x","article-title":"Spinal toxins can have persistent adverse effects","volume":"12","author":"Yaksh","year":"2011","journal-title":"Pain Med."},{"key":"10.1016\/j.toxicon.2020.02.008_bib108","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.3892\/mmr.2015.4647","article-title":"Role of nitric oxide synthase in the development of bone cancer pain and effect of L-NMMA","volume":"13","author":"Yang","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.toxicon.2020.02.008_bib109","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000370245","article-title":"Serious and long-term adverse events associated with the therapeutic and cosmetic use of botulinum toxin","volume":"95","author":"Yiannakopoulou","year":"2015","journal-title":"Pharmacology"},{"key":"10.1016\/j.toxicon.2020.02.008_bib110","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12640-013-9447-7","article-title":"Anti-inflammatory effects of botulinum toxin type a in a complete Freund's adjuvant-induced arthritic knee joint of hind leg on rat model","volume":"26","author":"Yoo","year":"2014","journal-title":"Neurotox. Res."},{"key":"10.1016\/j.toxicon.2020.02.008_bib111","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.biopha.2017.04.047","article-title":"Dexmedetomidine relieves formaldehyde-induced pain in rats through both \u03b12 adrenoceptor and imidazoline receptor","volume":"90","author":"Zhang","year":"2017","journal-title":"Biomed. Pharmacother."}],"container-title":["Toxicon"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010120300398?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010120300398?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T21:13:42Z","timestamp":1758575622000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041010120300398"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5]]},"references-count":106,"alternative-id":["S0041010120300398"],"URL":"https:\/\/doi.org\/10.1016\/j.toxicon.2020.02.008","relation":{},"ISSN":["0041-0101"],"issn-type":[{"value":"0041-0101","type":"print"}],"subject":[],"published":{"date-parts":[[2020,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"New analgesic: Focus on botulinum toxin","name":"articletitle","label":"Article Title"},{"value":"Toxicon","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxicon.2020.02.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}