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

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.

• Authors: Shannon D Shields, Daniel J Cavanaugh, Hyosang Lee, David J Anderson, Allan I Basbaum
• Journal: Pain (Pain) Vol. 151 Issue 2 Pg. 422-429 (Nov 2010) ISSN: 1872-6623 [Electronic] United States
• PMID: 20832171 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chemical References

• Mrgprd protein, mouse
• Plant Oils
• Receptors, G-Protein-Coupled
• TRPV Cation Channels
• TRPV1 protein, mouse
• Formaldehyde
• Caspases
• mustard oil

Topics

• Animals
• Behavior, Animal (drug effects)
• Caspases (administration & dosage)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Formaldehyde (adverse effects)
• Gene Expression Regulation (drug effects, genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mustard Plant (adverse effects)
• Nerve Fibers, Unmyelinated (metabolism, pathology)
• Nociceptors (pathology)
• Pain (chemically induced, genetics, pathology, physiopathology)
• Pain Measurement
• Plant Oils (adverse effects)
• Receptors, G-Protein-Coupled (deficiency, metabolism)
• Spinal Cord (pathology)
• TRPV Cation Channels (deficiency, metabolism)
• Time Factors