title: 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.affiliation: The Anesthesiology Department of Shanghai Sixth People's Hospital, Shanghai JiaoTong University, 600 Yi-Shan Road, Shanghai 200233, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ma
authors.forename: Quan-Hong
authors.initials: QH
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Dong-Ping
authors.initials: DP
authors.lastname: Du
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000068579:Celecoxib; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010812:Physical Stimulation; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D011720:Pyrazoles; D015222:Sodium Channels; D013449:Sulfonamides; C023790:tetrodotoxin-binding protein; D000068579:Celecoxib; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone