{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:22:53Z","timestamp":1789658573173,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T00:00:00Z","timestamp":1504051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Pain Knowledge Center Rotterdam\/Dutch Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Skin biopsies from patients with neuropathic pain often show changes in epidermal innervation, although it remains to be elucidated to what extent such changes can be linked to a particular subgroup of nerve fibers and how these changes are correlated with pain intensity. Here, we investigated to what extent behavioral signs of hyperalgesia are correlated with immunohistochemical changes of peptidergic and non\u2010peptidergic epidermal nerve fibers in a rat model of nerve injury\u2010induced pain. Rats subjected to unilateral partial ligation of the sciatic nerve developed significant mechanical and thermal hyperalgesia as tested by the withdrawal responses of the ipsilateral footpad to von Frey hairs and hotplate stimulation. At day 14, epidermal nerve fiber density and total epidermal nerve fiber length\/mm<jats:sup>2<\/jats:sup> were significantly and consistently reduced compared to the contralateral side, following testing and re\u2010testing by two blinded observers. The expression of calcitonin gene\u2010related peptide, a marker for peptidergic nerve fibers, was not significantly changed on the ipsilateral side. In contrast, the expression of the P2X<jats:sub>3<\/jats:sub> receptor, a marker for non\u2010peptidergic nerve fibers, was not only significantly reduced but could also be correlated with behavioral hyperalgesia. When labeling both peptidergic and non\u2010peptidergic nerve fibers with the pan\u2010neuronal marker PGP9.5, the expression was significantly reduced, albeit without a significant correlation with behavioral hyperalgesia. In conjunction, our data suggest that the pathology of the P2X<jats:sub>3<\/jats:sub> epidermal nerve fibers can be selectively linked to neuropathy, highlighting the possibility that it is the degeneration of these fibers that drives hyperalgesia.<\/jats:p>","DOI":"10.1002\/cne.24302","type":"journal-article","created":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T08:40:36Z","timestamp":1502959236000},"page":"3757-3768","source":"Crossref","is-referenced-by-count":14,"title":["The reduction of intraepidermal P2X<sub>3<\/sub> nerve fiber density correlates with behavioral hyperalgesia in a rat model of nerve injury\u2010induced pain"],"prefix":"10.1002","volume":"525","author":[{"given":"Malik","family":"Bechakra","sequence":"first","affiliation":[{"name":"Department of Neurology Erasmus MC Rotterdam The Netherlands"},{"name":"Department of Neuroscience Erasmus MC Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barthold N.","family":"Sch\u00fcttenhelm","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus MC Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Pederzani","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus MC Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter A.","family":"van Doorn","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus MC Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris I.","family":"de Zeeuw","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Erasmus MC Rotterdam The Netherlands"},{"name":"Netherlands Institute for Neuroscience, Royal Netherlands Academy for Arts &amp; Sciences Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8340-2755","authenticated-orcid":false,"given":"Joost L.M.","family":"Jongen","sequence":"additional","affiliation":[{"name":"Department of Neurology Erasmus MC Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1998.0719"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bja.a013473"},{"key":"e_1_2_9_4_1","volume-title":"Statistics at Square One","author":"Campbell M. 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