ABSTRACT
Objective]To investigate the change of spinal pro?inflammatory cytokines in a rat model of fentanyl induced acute hyperalgesia.[Methods]64 male SD rats were divided into 2 groups(n=32),fentanyl group and NS group. The rats were subcutaneously injected with fentanyl (60 μg/kg) or normal saline (1.2 mL/kg) 4 times with 15?minute intervals. Mechanical nociceptive thresholds and thermal nociceptive latency were measured via the tail pressure test(Tail flick thresholds,TFT) and paw withdrawal test(Paw withdrawal latency,PWL)on the day before,at 1,2,3,and 4 hour and on 1~5 day after injection. 4 rats were killed concomitantly and the lumber spinal cord were harvested to analysis the expression of NF-κB,PGE2,TNF-α,IL-1β,and IL-6.[Results]There were no significant changes of TFT,PWL and the expression of spinal inflammatory cytokines such as NF-κB, PGE2,IL-1β,and TNF-αcompared to baseline of rats treated with normal saline. The value of TFT ,PWL in fentanyl group raised to the highest(above the baseline)at the 1st hour after fentanyl injections and decreased thereafter,reached the lowest at the 1st day, raised increasinglyand up to baseline on the 3 day after injection. NF-κB,PGE2,IL-1β,and TNF-αincreased at the 4th hour,on 1 and 2 day and IL-6 increased at the 4 hour and onthe 1 day after fentanyl injections.[Conclusion]Subcutaneously injection of fentanyl induced significant mechanical and thermal hyperalgesia and increased spinal pro?inflammatory cytokines parallelly , indicated that fentanyl induced acute hyperalgesia is associated with spinal inflammatory reaction in rats.
ABSTRACT
Objective To investigate the inhibitant effects of parecoxib, a cyclooxygenase-2 (COX-2) inhibitor, in acute fentanyl induced hyperalgesia in rats. Methods (1) Thirty SD rats (n=6 for each group) were subcutaneously injected with fentanyl (40 μg/kg × 4 times with a 15 min-interval) or saline to establish acute fentanyl induced hyperalgesia model, andparecoxib (5, 10 mg/kg) was administrated intraperitoneally in parecoxib group. Mechanical nociceptive thresholds were measured by the tail pressure test every hour during 1~4 hours and once a day during 1~5 days. (2) 24 SD rats (n = 6 foreach group) were subcutaneously injected with fentanyl as above described and randomly administrated intraperitoneally with parecoxib in 10 mg/kg in 15 min before and at the 4th hour and the 1st day after fentanyl injection except rats in the control group, mechanical nociceptive thresholds were measured by the tail pressure test at time points as above described. Results (1)Acute high dose fentanyl injection induced mechanical hyperalgesia and parecoxib (at 5 or 10 mg/kg)inhibited fentanyl induced hyperalgesia in rats. (2)Parecoxib inhibited fentanyl induced hyperalgesia at 15 min before and at the 4th hour after, but not on the 1st day after fentanyl injection. Conclusions This study provides the first evidence that subanalgesia doses of parecoxib had inhibitory effects on acute fentanyl induced hyperalgesia in time-dependent manners in rats.