{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:51:01Z","timestamp":1790524261487,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T00:00:00Z","timestamp":1539648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Gr\u00fcnenthal GmbH"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Nociceptin\/orphanin FQ opioid peptide (NOP)\u2010receptor (NOP\u2010R) is a member of the opioid receptor family. NOP\u2010R activation has demonstrated analgesic effects in preclinical pain models without the addiction risks associated with other opiate targets. Pachyonychia congenita (PC) is a palmoplantar keratoderma characterized by neuropathic pain in affected skin. A cohort of <jats:italic>KRT6A<\/jats:italic> gene mutation PC patients with no other explanation for their neuropathic pain offered a unique opportunity to assess potential of NOP\u2010R as a therapeutic target. Plantar biopsies from 10 PC patients and 10 age\/gender matched controls were performed at the ball (PC\u2010affected) and the arch (PC\u2010unaffected) of the foot. NOP\u2010R expression was assessed by immunohistochemistry. Localization of NOP\u2010R in subsets of epidermal nerve fibers was investigated using the pan\u2010neuronal marker PGP9.5, markers for unmyelinated peptidergic fibers (calcitonin gene\u2010related peptide [CGRP] and substance P [SP]), as well as for myelinated A\u03b4 and A\u03b2 fibers (neurofilament H [NFH]). Robust NOP\u2010R expression was detected in epidermal keratinocytes and in a subset of PGP9.5+ fibers in both epidermis and dermis, confirmed by western blot and absorption experiments with NOP\u2010R peptide. NOP\u2010R expression in keratinocytes was significantly reduced in PC\u2010affected plantar skin compared with PC\u2010unaffected skin. In addition, NOP\u2010R expression occurred in dermal NFH+ myelinated fibers in all groups, although few CGRP+ fibers co\u2010expressed NOP\u2010R. Furthermore, most SP+ fibers also co\u2010expressed NOP\u2010R. These findings indicate that NOP\u2010R is expressed on epidermal keratinocytes, as well as on epidermal and dermal nerve fibers and has potential as a promising target to treat neuropathic pain in PC.<\/jats:p>","DOI":"10.1111\/jns.12288","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T01:38:49Z","timestamp":1537925929000},"page":"241-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nociceptin\/orphanin FQ opioid peptide\u2010receptor expression in pachyonychia congenita"],"prefix":"10.1111","volume":"23","author":[{"given":"Baohan","family":"Pan","sequence":"first","affiliation":[{"name":"Neurology The Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Translational Science &amp; Intelligence Gr\u00fcnenthal GmbH  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Jostock","sequence":"additional","affiliation":[{"name":"In\u2010Vitro Biology &amp; 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