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

Weiguo Zhu, Pin Xu, Fernando X. Cuascut, Alison K. Hall, Gerry S. Oxford

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13770-13780
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number50
DOIs
StatePublished - Dec 12 2007

Fingerprint

TRPV Cation Channels
Activins
Hyperalgesia
Spinal Ganglia
Sensory Receptor Cells
Neurons
Activin Receptors
Capsaicin
Sensory Ganglia
Pain
1-Phosphatidylinositol 4-Kinase
Extracellular Signal-Regulated MAP Kinases
Protein Kinases
Hypersensitivity
Phosphotransferases
Pharmacology
Peptides
Wounds and Injuries

Keywords

  • Activin
  • Capsaicin
  • Hyperalgesia
  • Nociceptor
  • Pain
  • TRPV1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activin acutely sensitizes dorsal root ganglion neurons and induces hyperalgesia via PKC-mediated potentiation of transient receptor potential vanilloid I. / Zhu, Weiguo; Xu, Pin; Cuascut, Fernando X.; Hall, Alison K.; Oxford, Gerry S.

In: Journal of Neuroscience, Vol. 27, No. 50, 12.12.2007, p. 13770-13780.

Research output: Contribution to journalArticle

Zhu, Weiguo ; Xu, Pin ; Cuascut, Fernando X. ; Hall, Alison K. ; Oxford, Gerry S. / Activin acutely sensitizes dorsal root ganglion neurons and induces hyperalgesia via PKC-mediated potentiation of transient receptor potential vanilloid I. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 50. pp. 13770-13780.
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