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Pain behavior in the formalin test persists after ablation of the great majority of C-fiber nociceptors

Shields, Shannon D. and Cavanaugh, Daniel J. and Lee, Hyosang and Anderson, David J. and Basbaum, Allan I. (2010) Pain behavior in the formalin test persists after ablation of the great majority of C-fiber nociceptors. Pain, 151 (2). pp. 422-429. ISSN 0304-3959.

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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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Additional Information:© 2010 International Association for the Study of Pain. Published by Elsevier B.V. PMID: 20832171. Received 28 April 2010; revised 31 July 2010; accepted 3 August 2010. Available online 15 September 2010. This work was supported in part by NIH PO1NS048499 to DJA and AIB, NIH NS14627 to AIB and by a grant from the Christopher and Dana Reeve Foundation to HL. The authors declare no conflict of interest.
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Subject Keywords:Formalin test; TRPV1; MrgprD; Ablation; Primary afferent; Fos; Behavior
Record Number:CaltechAUTHORS:20101104-074429356
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:20657
Deposited By: Ruth Sustaita
Deposited On:04 Nov 2010 15:15
Last Modified:26 Dec 2012 12:35

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