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

H Richard Koerber,Sacha A Malin,Brian M Davis,Collene E Anderson,Michael P Jankowski,Sabrina L Mcilwrath,Jeffrey J Lawson

doi:10.1186/1744-8069-6-58

H Richard Koerber, Sacha A Malin + Show 5 more

Open Access

https://doi.org/10.1186/1744-8069-6-58

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Journal: Molecular pain	Publication Date: Jan 1, 2010
Citations: 98	License type: cc-by

Affiliation: University of Pittsburgh

Abstract

BackgroundPrevious 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.ResultsIn 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.ConclusionsResults 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.

Highlights

The transient receptor potential vanilloid type 1 (TRPV1) ion channel is activated by a variety of stimuli including capsaicin, heat, acidic pH and anandamide [1,2,3,4]
TRPV1 channel function can be modulated by numerous endogenous compounds released following injury, or inflammation including ATP, histamine, bradykinin, various cytokines and numerous growth factors such as NGF and artemin that are upregulated in the skin following inflammation [5]
C-fibers were further divided based on their peripheral response properties to mechanical and thermal stimuli [10]. These groups included: fibers that responded to mechanical and heat and sometimes cold stimuli (CPM); C-mechanocold (CMC) fibers responded to mechanical and cold stimuli on the cutaneous receptive field (RF); C-mechano (CM) fibers responded to mechanical but not to thermal stimulation of the skin; C-cold (CC) fibers responded only to cold/cooling and not to mechanical or heat stimuli; C-heat (CH) fibers responded to heat, but not to mechanical or cold stimuli

Summary

Introduction

The transient receptor potential vanilloid type 1 (TRPV1) ion channel is activated by a variety of stimuli including capsaicin, heat, acidic pH and anandamide [1,2,3,4]. In uninjured murine fibers innervating hairy skin, TRPV1 is localized in a subpopulation of C-fiber nociceptors that respond to heat (CH-fibers) but not mechanical or cold stimuli [10,11]. The majority of C-fibers innervating the skin are C-polymodal (CPM) afferents responding to both mechanical and thermal stimuli, the vast majority of which have been shown to be non-peptidergic IB4 positive fibers that lack TRPV1 [10,12]. In TRPV1-/- mice these CPM fibers exhibit normal heat responses [12] they lack functional CH fibers [10]. 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

Methods

Results

Conclusion