Activin acutely sensitizes dorsal root ganglion neurons and induces hyperalgesia via PKC-mediated potentiation of transient receptor potential vanilloid I

Document Type

Journal Article

Publication Date

12-12-2007

Journal

Journal of Neuroscience

Volume

27

Issue

50

DOI

10.1523/JNEUROSCI.3822-07.2007

Keywords

Activin; Capsaicin; Hyperalgesia; Nociceptor; Pain; TRPV1

Abstract

Pain hypersensitivity is a cardinal sign of tissue damage, but how molecules from peripheral tissues affect sensory neuron physiology is incompletely understood. Previous studies have shown that activin A increases after peripheral injury and is sufficient to induce acute nociceptive behavior and increase pain peptides in sensory ganglia. This study was designed to test the possibility that the enhanced nociceptive responsiveness associated with activin involved sensitization of transient receptor potential vanilloid I (TRPV1) in primary sensory neurons. Activin receptors were found widely distributed among adult sensory neurons, including those that also express the capsaicin receptor. Whole-cell patch-clamp recording from sensory neurons showed that activin acutely sensitized capsaicin responses and depended on activin receptor kinase activity. Pharmacological studies revealed that the activin sensitization of capsaicin responses required PKCε signaling, but not PI3K (phosphoinositide 3-kinase), ERK (extracellular signal-regulated protein kinase), PKA, PKCα/β, or Src. Furthermore, activin administration caused acute thermal hyperalgesia in wild-type mice, but not in TRPV1-null mice. These data suggest that activin signals through its own receptor, involves PKCε signaling to sensitize the TRPV1 channel, and contributes to acute thermal hyperalgesia. Copyright © 2007 Society for Neuroscience.

This document is currently not available here.

Share

COinS