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

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.

• Authors: Ke Ma, Quan-Hong Zhou, Jin Chen, Dong-Ping Du, Yonghua Ji, Wei Jiang
• Journal: Brain research (Brain Res) Vol. 1209 Pg. 57-64 (May 13 2008) ISSN: 0006-8993 [Print] Netherlands
• PMID: 18400213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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