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Citation
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HERO ID
6111102
Reference Type
Journal Article
Title
Pain behavior in the formalin test persists after ablation of the great majority of C-fiber nociceptors
Author(s)
Shields, SD; Cavanaugh, DJ; Lee, H; Anderson, DJ; Basbaum, AI
Year
2010
Is Peer Reviewed?
1
Journal
Pain
ISSN:
0304-3959
EISSN:
1872-6623
Volume
151
Issue
2
Page Numbers
422-429
Language
English
PMID
20832171
DOI
10.1016/j.pain.2010.08.001
Abstract
Although the formalin test is a widely used model of persistent pain, the primary afferent fiber types that underlie the cellular and behavioral responses to formalin injection are largely unknown. Here we used a combined genetic and pharmacological approach to investigate the effect of ablating subsets of primary afferent nociceptors on formalin-induced nocifensive behaviors and spinal cord Fos protein expression. Intrathecal capsaicin-induced ablation of the central terminals of TRPV1+neurons greatly reduced the behavioral responses and Fos elicited by low-dose (0.5%) formalin. In contrast, genetic ablation of the MrgprD-expressing subset of non-peptidergic unmyelinated afferents, which constitute a largely non-overlapping population, altered neither the behavior nor the Fos induced by low-dose formalin. Remarkably, nocifensive behavior following high-dose (2%) formalin was unchanged in mice lacking either afferent population, or even in mice lacking both populations, which together make up the great majority of C-fiber nociceptors. Thus, at high doses, which are routinely used in the formalin test, formalin-induced "pain" behavior persists in the absence of the vast majority of C-fiber nociceptors, which points to a contribution of a large spectrum of afferents secondary to non-specific formalin-induced tissue and nerve damage.
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