Involvement of subtypes γ and ε of protein kinase C in colon pain induced by formalin injection

Neurosignals. 2011;19(3):142-50. doi: 10.1159/000328311. Epub 2011 Jun 23.

Abstract

Protein kinase C (PKC) has been widely reported to participate in somatic pain; however, its role in visceral pain remains largely unclear. Using a colon inflammatory pain model by intracolonic injection of formalin in rats, the present study was to examine the role of PKC in visceral pain and determine which subtypes may be involved. The colon pain behavior induced by formalin injection could be enhanced by intrathecal pretreatment with a PKC activator (PMA), and alleviated by a PKC inhibitor (H-7). Wide dynamic range (WDR) neurons in the L6-S1 spinal dorsal horn that were responsive to colorectal distension were recorded extracellularly. It was found that neuronal activity was greatly increased following formalin injection. Microdialysis of PMA near the recorded neuron in the spinal dorsal horn facilitated the enhanced responsive activity induced by formalin injection, while H-7 inhibited significantly the enhanced response induced by formalin injection. Western blot analysis revealed that membrane translocation of PKC-γ and PKC-ε, but not other subtypes, in the spinal cord was obviously increased following formalin injection. Therefore, our findings suggest that PKC is actively involved in the colon pain induced by intracolonic injection of formalin. PKC-γ and PKC-ε subtypes seem to significantly contribute to this process.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage
  • Analysis of Variance
  • Animals
  • Colonic Diseases / chemically induced
  • Colonic Diseases / complications
  • Disease Models, Animal
  • Drug Interactions
  • Enzyme Activation / drug effects
  • Enzyme Activators / pharmacology
  • Enzyme Inhibitors / administration & dosage
  • Evoked Potentials / drug effects
  • Formaldehyde / adverse effects*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Male
  • Protein Kinase C / metabolism*
  • Protein Kinase C-epsilon / metabolism*
  • Rats
  • Rats, Wistar
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Tetradecanoylphorbol Acetate / administration & dosage
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Time Factors
  • Visceral Pain / chemically induced*
  • Visceral Pain / complications
  • Visceral Pain / pathology

Substances

  • Enzyme Activators
  • Enzyme Inhibitors
  • Formaldehyde
  • phorbolol myristate acetate
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • protein kinase C gamma
  • Protein Kinase C
  • Protein Kinase C-epsilon
  • Tetradecanoylphorbol Acetate