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Cutaneous C-polymodal fibers lacking TRPV1 are sensitized to heat following inflammation, but fail to drive heat hyperalgesia in the absence of TPV1 containing C-heat fibers

Koerber, HR and McIlwrath, SL and Lawson, JJ and Malin, SA and Anderson, CE and Jankowski, MP and Davis, BM (2010) Cutaneous C-polymodal fibers lacking TRPV1 are sensitized to heat following inflammation, but fail to drive heat hyperalgesia in the absence of TPV1 containing C-heat fibers. Molecular Pain, 6. ISSN 1744-8069

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Abstract

Background: Previous studies have shown that the TRPV1 ion channel plays a critical role in the development of heat hyperalgesia after inflammation, as inflamed TRPV1-/- mice develop mechanical allodynia but fail to develop thermal hyperalgesia. In order to further investigate the role of TRPV1, we have used an ex vivo skin/nerve/DRG preparation to examine the effects of CFA-induced-inflammation on the response properties of TRPV1-positive and TRPV1-negative cutaneous nociceptors.Results: In wildtype mice we found that polymodal C-fibers (CPMs) lacking TRPV1 were sensitized to heat within a day after CFA injection. This sensitization included both a drop in average heat threshold and an increase in firing rate to a heat ramp applied to the skin. No changes were observed in the mechanical response properties of these cells. Conversely, TRPV1-positive mechanically insensitive, heat sensitive fibers (CHs) were not sensitized following inflammation. However, results suggested that some of these fibers may have gained mechanical sensitivity and that some previous silent fibers gained heat sensitivity. In mice lacking TRPV1, inflammation only decreased heat threshold of CPMs but did not sensitize their responses to the heat ramp. No CH-fibers could be identified in naïve nor inflamed TRPV1-/- mice.Conclusions: Results obtained here suggest that increased heat sensitivity in TRPV1-negative CPM fibers alone following inflammation is insufficient for the induction of heat hyperalgesia. On the other hand, TRPV1-positive CH fibers appear to play an essential role in this process that may include both afferent and efferent functions. © 2010 Koerber et al; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Koerber, HRrkoerber@pitt.eduRKOERBER
McIlwrath, SL
Lawson, JJ
Malin, SA
Anderson, CE
Jankowski, MP
Davis, BMbmd1@pitt.eduBMD1
Date: 21 September 2010
Date Type: Publication
Journal or Publication Title: Molecular Pain
Volume: 6
DOI or Unique Handle: 10.1186/1744-8069-6-58
Schools and Programs: School of Medicine > Medicine
School of Medicine > Neurobiology
Refereed: Yes
ISSN: 1744-8069
Date Deposited: 14 Nov 2016 20:21
Last Modified: 04 Feb 2019 16:55
URI: http://d-scholarship.pitt.edu/id/eprint/30234

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