TTX-R Na+ current-reduction by celecoxib correlates with changes in PGE(2) and CGRP within rat DRG neurons during acute incisional pain

Brain Res. 2008 May 13;1209:57-64. doi: 10.1016/j.brainres.2008.02.096. Epub 2008 Mar 18.

Abstract

The present study was undertaken to investigate whether celecoxib could regulate the tetrodotoxin-resistant (TTX-R) sodium channel current in rat dorsal root ganglia (DRG) and whether prostaglandin E2 (PGE2) and calcitonin gene-related protein (CGRP) were involved in celecoxib's analgesia during acute incisional pain. Seventy-five rats were randomly allocated into three groups. Group A was the control group receiving a placebo (sugar pill) 1 h before and 12 h after surgery (right hind paw incisional pain). Group B was the test group receiving celecoxib 30 mg/kg orally 1 h before and 12 h after surgery. Group C was the naive group receiving a sham operation. The changes in the mechanical withdrawal thresholds, PGE2 and CGRP concentration in incisional paw tissue and DRG, and total TTX-R sodium channel current density in small DRG neurons were investigated 1 h before the operation and 2 h, 6 h, 12 h, 24 h, 48 h and 96 h after the operation. The results showed both of a decrease in mechanical withdrawal thresholds and an increase of TTX-R sodium channel current density in DRG neurons in group B were significantly lower than those of group A at 24 h and 48 h after the operation (P<0.05). The increase in PGE2 and CGRP concentrations at incisional paw tissue and DRG neurons in group B were lower than those of groups A at 24 h and 48 h after the operation (P<0.05). This study indicates that: 1) celecoxib can inhibit TTX-R sodium channel current density in rat DRG neurons; 2) PGE2 and CGRP participate in celecoxib's analgesic effect on acute incisional pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Celecoxib
  • Cells, Cultured
  • Dinoprostone / metabolism
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / physiopathology
  • Male
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / metabolism
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain, Postoperative / drug therapy*
  • Pain, Postoperative / metabolism
  • Pain, Postoperative / physiopathology
  • Physical Stimulation
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channels / drug effects*
  • Sodium Channels / metabolism
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Pyrazoles
  • Sodium Channels
  • Sulfonamides
  • tetrodotoxin-binding protein
  • Celecoxib
  • Calcitonin Gene-Related Peptide
  • Dinoprostone