{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:31:11Z","timestamp":1768869071545,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"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>Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject.<\/jats:p>","DOI":"10.3390\/toxins18010050","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T11:35:27Z","timestamp":1768822527000},"page":"50","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Botulinum Toxin Treatment of Notalgia Paresthetica\u2014A Critical Review and Update"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5864-4300","authenticated-orcid":false,"given":"Ava Grace","family":"Tohidian","sequence":"first","affiliation":[{"name":"Royal College of Surgeons, School of Medicine, D02 YN77 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahroo","family":"Etemadmoghadam","sequence":"additional","affiliation":[{"name":"Glenn Biggs Institute, University of Texas Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-8730","authenticated-orcid":false,"given":"Bahman","family":"Jabbari","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06519, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"adv39941","DOI":"10.2340\/actadv.v104.39941","article-title":"Notalgia Paresthetica Dermatologist Report of Symptom Burden and Treatment: Results from a Physician Survey","volume":"104","author":"Kim","year":"2024","journal-title":"Acta Derm. Venereol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1056\/NEJMoa2210699","article-title":"KOMFORT Trial Investigators. Phase 2 Trial of Difelikefalin in Notalgia Paresthetica","volume":"388","author":"Kim","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1001\/jama.2024.4899","article-title":"Chronic Pruritus: A Review","volume":"331","author":"Butler","year":"2024","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/ijd.13853","article-title":"Notalgia paresthetica: A review for dermatologists","volume":"57","author":"Howard","year":"2018","journal-title":"Int. J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"M\u00fclko\u011flu, C., and Nac\u0131r, B. (2020). Notalgia paresthetica: Clinical features, radiological evaluation, and a novel therapeutic option. BMC Neurol., 20.","DOI":"10.1186\/s12883-020-01773-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S1474-4422(18)30217-5","article-title":"Clinical presentation, management, and pathophysiology of neuropathic itch","volume":"17","author":"Steinhoff","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"86","DOI":"10.5021\/ad.2016.28.1.86","article-title":"Considerable Variability in the Efficacy of 8% Capsaicin Topical Patches in the Treatment of Chronic Pruritus in 3 Patients with Notalgia Paresthetica","volume":"28","author":"Andersen","year":"2016","journal-title":"Ann. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00403-024-03535-7","article-title":"Neural therapy in notalgia paresthetica","volume":"317","year":"2024","journal-title":"Arch. Dermatol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1097\/PHM.0000000000000946","article-title":"Physical Medicine and Rehabilitation Role on Notalgia Paresthetica: Case Report and Treatment Review","volume":"97","author":"Antunes","year":"2018","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3390\/clinpract13010029","article-title":"Notalgia Paresthetica Review: Update on Presentation, Pathophysiology, and Treatment","volume":"13","author":"Robinson","year":"2023","journal-title":"Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11916-025-01402-2","article-title":"Notalgia Paresthetica: An Updated Review of Pathophysiology, Diagnosis, and Treatment Approaches","volume":"29","author":"Nguyen","year":"2025","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/WNF.0b013e3181672225","article-title":"Relief of intractable pruritus after administration of botulinum toxin A (botox): A case report","volume":"31","author":"Salardini","year":"2008","journal-title":"Clin. Neuropharmacol."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1001\/archderm.143.8.980","article-title":"Successful treatment of notalgia paresthetica with botulinum toxin type A","volume":"143","author":"Weinfeld","year":"2007","journal-title":"Arch. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1365-2133.2010.09783.x","article-title":"Botulinum toxin type A for neuropathic itch","volume":"163","author":"Wallengren","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ad.2013.09.003","article-title":"Notalgia paresthetica: Treatment using intradermal botulinum toxin A","volume":"105","author":"Allegue","year":"2014","journal-title":"Actas Dermosifiliogr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.jaad.2013.12.006","article-title":"Treatment of notalgia paresthetica with botulinum toxin A: A double-blind randomized controlled trial","volume":"70","author":"Maari","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.rh.2019.07.004","article-title":"Notalgia parest\u00e9sica, tratamiento con toxina botul\u00ednica tipo A [Notalgia paresthetica: Treatment with botulinum toxin type A]","volume":"54","year":"2020","journal-title":"Rehabilitacion"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/CND.0000000000000276","article-title":"Use of Botulinum Toxin Type A in a Patient With Refractory Itch From Notalgia Paresthetica","volume":"21","author":"Datta","year":"2020","journal-title":"J. Clin. Neuromuscul. Dis."},{"key":"ref_20","first-page":"45","article-title":"Case report and short review: Botulinum toxin injection for the treatment of Notalgia parasthetica","volume":"38","author":"Sharad","year":"2020","journal-title":"J. Appl. Cosmetol."},{"key":"ref_21","first-page":"e96000","article-title":"Botulinum Toxin for the Treatment of Chronic Notalgia Paresthetica: A Case Report","volume":"17","author":"Moreno","year":"2025","journal-title":"Cureus"},{"key":"ref_22","first-page":"721","article-title":"Notalgia Paresthetica","volume":"57","author":"Franceschi","year":"2018","journal-title":"Acta Clin. Croat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/brain\/awt158","article-title":"The neurology of itch","volume":"137","author":"Dhand","year":"2014","journal-title":"Brain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"adv44444","DOI":"10.2340\/actadv.v105.44444","article-title":"Prevalence of Central Sensitization in Notalgia Paresthetica Patients and its Association with Vertebral Degeneration: A Cross-sectional Study","volume":"105","author":"Cirakoglu","year":"2025","journal-title":"Acta Derm. Venereol."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"108237","DOI":"10.1016\/j.toxicon.2025.108237","article-title":"An update on botulinum toxin treatment of painful diabetic neuropathy, post-traumatic painful neuropathy\/neuralgia, post-herpetic neuralgia and occipital neuralgia","volume":"255","author":"Jabbari","year":"2025","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1186\/s40064-016-2071-2","article-title":"Central antinociceptive activity of peripherally applied botulinum toxin type A in lab rat model of trigeminal neuralgia","volume":"5","author":"Wu","year":"2016","journal-title":"Springerplus"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2340\/00015555-1344","article-title":"Notalgia paraesthetica: A descriptive two-cohort study of 65 patients from Brazil and Germany","volume":"92","author":"Huesmann","year":"2012","journal-title":"Acta Derm. Venereol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bai, J.Q.A., Ding, M., Dienes, S., and Mukovozov, I. (2025). Efficacy and safety of treatments for notalgia paresthetica: A systematic review. J. Eur. Acad. Dermatol. Venereol.","DOI":"10.1111\/jdv.70222"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"392","DOI":"10.5021\/ad.2014.26.3.392","article-title":"Neuropathic itch of the back: A case of notalgia paresthetica","volume":"26","author":"Shin","year":"2014","journal-title":"Ann. Dermatol."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1423-0127-19-77","article-title":"Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis","volume":"19","author":"Izumi","year":"2012","journal-title":"J. Biomed. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1097\/WNR.0000000000000779","article-title":"Long-term anti-itch effect of botulinum neurotoxin A is associated with downregulation of TRPV1 and TRPA1 in the dorsal root ganglia in mice","volume":"28","author":"Cao","year":"2017","journal-title":"Neuroreport"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jdermsci.2018.12.004","article-title":"Botulinum toxin blocks mast cells and prevents rosacea like inflammation","volume":"93","author":"Choi","year":"2019","journal-title":"J. Dermatol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ghaseminejad-Bandpey, A., Etemadmoghadam, S., and Jabbari, B. (2024). Botulinum Toxin Treatment of Psoriasis-A Comprehensive Review. Toxins, 16.","DOI":"10.3390\/toxins16100449"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1038\/jid.2012.60","article-title":"Botulinum neurotoxin A decreases infiltrating cutaneous lymphocytes and improves acanthosis in the KC-Tie2 mouse model","volume":"132","author":"Ward","year":"2012","journal-title":"J. Investg. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jdermsci.2020.11.003","article-title":"Suppression of neuropeptide by botulinum toxin improves imiquimod-induced psoriasis-like dermatitis via the regulation of neuroimmune system","volume":"101","author":"Amalia","year":"2021","journal-title":"J. Dermatol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Brin, M.F., Nelson, M., Ashourian, N., Brideau-Andersen, A., and Maltman, J. (2024). Update on Non-Interchangeability of Botulinum Neurotoxin Products. Toxins, 16.","DOI":"10.3390\/toxins16060266"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Martina, E., Diotallevi, F., Radi, G., Campanati, A., and Offidani, A. (2021). Therapeutic Use of Botulinum Neurotoxins in Dermatology: Systematic Review. Toxins, 13.","DOI":"10.3390\/toxins13020120"},{"key":"ref_41","first-page":"109","article-title":"Report on 25 Notalgia paresthetica cases: Clinical features and treatments","volume":"34","author":"Karasel","year":"2022","journal-title":"Agri"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1080\/09546634.2019.1603360","article-title":"Notalgia paresthetica: Treatment review and algorithmic approach","volume":"31","author":"Ansari","year":"2020","journal-title":"J. Dermatol. Treat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e13723","DOI":"10.1111\/srt.13723","article-title":"A systematic review of procedural modalities in the treatment of notalgia paresthetica","volume":"30","author":"Nilforoushzadeh","year":"2024","journal-title":"Skin. Res. Technol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00403-024-03624-7","article-title":"An update to clinical effectiveness of botulinum toxin injection in treating notalgia paresthetica: Hopes and pitfalls","volume":"317","author":"Hatami","year":"2024","journal-title":"Arch. Dermatol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/ajd.12412","article-title":"Notalgia paraesthetica: A pilot study of treatment with simple exercises and stretches","volume":"57","author":"Zagarella","year":"2016","journal-title":"Australas. J. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/ajd.12702","article-title":"Treatment of notalgia paraesthetica with manipulative physiotherapy","volume":"59","author":"Sahhar","year":"2018","journal-title":"Australas. J. Dermatol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/1\/50\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T11:43:53Z","timestamp":1768823033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/1\/50"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,19]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["toxins18010050"],"URL":"https:\/\/doi.org\/10.3390\/toxins18010050","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,19]]}}}