{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:59:21Z","timestamp":1784257161728,"version":"3.55.0"},"reference-count":89,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T00:00:00Z","timestamp":1547683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Trigeminal neuralgia is difficult to treat and shows upregulation of sodium channels. The expectorant ambroxol acts as a strong local anesthetic, about 40 times stronger than lidocaine. It preferentially inhibits the channel subtype Na\n                      <jats:sub>v<\/jats:sub>\n                      1.8, expressed especially in nociceptive C\u2010fibers. It seemed reasonable to try ambroxol for the treatment with neuropathic facial pain unresponsive to other standard options.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>Medical records of patients suffering from classical trigeminal neuralgia (n\u00a0=\u00a05) and successful pain reduction following topical ambroxol 20% cream in addition to standard treatment are reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All patients reported pain attacks with pain intensity between 4 and 10 NRS (numeric pain scale). In all cases they could be triggered, 3 patients reported additional spontaneous pain. Attacks were reduced in all 5 patients. Pain reduction achieved following ambroxol 20% cream was 2\u20138 points (NRS) earliest within 15\u201330\u00a0minutes and lasted for 4\u20136\u00a0hours mostly. This was reproducible in all cases; in one case pain was eliminated after 1\u00a0week. No patient reported side effects or skin changes; oral medication was reduced in 2 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>For the first time, a clinically significant pain relief following topical ambroxol 20% cream in patients with trigeminal neuralgia is reported. In view of the positive side effect profile, topical ambroxol for patients with such a highly impaired quality of life should be investigated further as a matter of urgency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.13475","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T13:08:51Z","timestamp":1547730531000},"page":"418-429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Topical Ambroxol 20% for the Treatment of Classical Trigeminal Neuralgia \u2013 A New Option? Initial Clinical Case Observations"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8505-0346","authenticated-orcid":false,"given":"Kai\u2010Uwe","family":"Kern","sequence":"first","affiliation":[{"name":"Institute for Pain Medicine\/Pain Practice Wiesbaden Wiesbaden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Schwickert\u2010Nieswandt","sequence":"additional","affiliation":[{"name":"Institute for Pain Medicine\/Pain Practice Wiesbaden Wiesbaden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Maih\u00f6fner","sequence":"additional","affiliation":[{"name":"Department of Neurology General Hospital F\u00fcrth F\u00fcrth Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charly","family":"Gaul","sequence":"additional","affiliation":[{"name":"Migraine and Headache Clinic K\u00f6nigstein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1177\/0333102413485658","article-title":"The International Classification of Headache Disorders, 3rd edition (beta version)","volume":"33","author":"Headache Classification Committee of the International Headache Society","year":"2013","journal-title":"Cephalalgia"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1212\/WNL.0000000000002840","article-title":"Trigeminal neuralgia: New classification and diagnostic grading for practice and research","volume":"87","author":"Cruccu G","year":"2016","journal-title":"Neurology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"The International Classification of Headache Disorders, 3rd edition","volume":"38","author":"Headache Classification Committee of the International Headache Society (IHS)","year":"2018","journal-title":"Cephalalgia"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1186\/s10194-015-0563-z","article-title":"Comparison of tolerability and adverse symptoms in oxcarbazepine and carbamazepine in the treatment of trigeminal neuralgia and neuralgiform headaches using the Liverpool Adverse Events Profile (AEP)","volume":"16","author":"Besi E","year":"2015","journal-title":"J Headache Pain"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s10194-016-0651-8","article-title":"Therapeutic efficacy and safety of botulinum toxin A therapy in trigeminal neuralgia: A systematic review and meta\u2010analysis of randomized controlled trials","volume":"17","author":"Morra ME","year":"2016","journal-title":"J Headache Pain"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S1474-4422(17)30005-4","article-title":"Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: A double\u2010blind, placebo\u2010controlled, randomised withdrawal phase 2a trial","volume":"16","author":"Zakrzewska JM","year":"2017","journal-title":"Lancet Neurol"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2016.00131"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.neuroscience.2009.08.037","article-title":"Abnormal expression of voltage\u2010gated sodium channels Nav1.7, Nav1.3 and Nav1.8 in trigeminal neuralgia","volume":"164","author":"Siqueira SR","year":"2009","journal-title":"Neuroscience"},{"key":"e_1_2_8_10_1","first-page":"72","article-title":"The role of Nav1.9 channel in the development of neuropathic orofacial pain associated with trigeminal neuralgia","volume":"11","author":"Luiz AP","year":"2015","journal-title":"Mol Pain"},{"issue":"3","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1007\/s00482-015-0060-y","article-title":"Topical ambroxol for the treatment of neuropathic pain. 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