The reduction of intraepidermal P2X3 nerve fiber density correlates with behavioral hyperalgesia in a rat model of nerve injury-induced pain
Autor: | Chris I. De Zeeuw, Barthold N. Schüttenhelm, Pieter A. van Doorn, Tiziana Pederzani, Malik Bechakra, Joost L M Jongen |
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Přispěvatelé: | Neurology, Neurosciences, Netherlands Institute for Neuroscience (NIN) |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Sciatica Pathology medicine.medical_specialty integumentary system General Neuroscience Nerve fiber Anatomy Calcitonin gene-related peptide Nerve injury Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Threshold of pain Hyperalgesia Neuropathic pain Journal Article medicine Sciatic nerve medicine.symptom 030217 neurology & neurosurgery |
Zdroj: | Journal of Comparative Neurology, 525(17), 3757-3768. Wiley-Liss Inc. Journal of Comparative Neurology, 525, 3757-3768. Wiley-Liss Inc. |
ISSN: | 0021-9967 |
Popis: | 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-peptidergic epidermal nerve fibers in a rat model of nerve injury-induced 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 (IENFD) and total epidermal nerve fiber length/mm(2) (ENFL) were significantly and consistently reduced compared to the contralateral side, following testing and re-testing by two blinded observers. The expression of calcitonin gene-related peptide (CGRP), a marker for peptidergic nerve fibers, was not significantly changed on the ipsilateral side. In contrast, the expression of the P2X3 receptor, a marker for non-peptidergic nerve fibers, was not only significantly reduced but could also be correlated with behavioral hyperalgesia. When labeling both peptidergic and non-peptidergic nerve fibers with the pan-neuronal 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 P2X3 epidermal nerve fibers can be selectively linked to neuropathy, highlighting the possibility that it is the degeneration of these fibers that drives hyperalgesia. This article is protected by copyright. All rights reserved. |
Databáze: | OpenAIRE |
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