Role of spinal peroxynitrite in remifentanil-induced hyperalgesia in rats

Abstract

Objective To evaluate the role of spinal peroxynitrite in remifentanil-induced hyperalgesia in rats. Methods Thirty-two male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were randomly divided into 4 groups(n=8 each)using a random number table: control group(group C), remifentanil group(group R), hydrogen-rich saline group(group C+ H), and remifentanil + hydrogen-rich saline group(group R+ H). In group C, normal saline was infused for 60 min at a rate of 0.1 ml·kg-1·min-1.In group R, remifentanil was infused for 60 min at a rate of 1.0 μg·kg-1·min-1.In group R+ H, remifentanil was infused for 60 min at a rate of 1.0 μg·kg-1·min-1, and hydrogen-rich saline 10 ml/kg was intraperitoneally injected at 10 min before iv infusion.At 24 h before iv infusion and 6, 24 and 48 h after iv infusion(T0-3), the mechanical paw withdrawal threshold(MWT)and thermal paw withdrawal latency(TWL)were measured.All the rats were sacrificed after the last measurement of pain thresholds, the lumbar segment(L4-6)of the spinal cord was removed for determination of the nitrated manganese superoxide dismutase(MnSOD)expression(by immunoprecipitation and Western blot analysis), 3-nitrotyrosine(3-NT)expression(by Western blot)and spinal MnSOD activity(by spectrophotometer). Results Compared with group C, the MWT was significantly decreased, and TWL was shortened at T1-T3, the expression of spinal 3-NT and nitrated MnSOD was up-regulated, and MnSOD activity was decreased in R and R+ H groups, and no significant change was found in the parameters mentioned above in group C+ H.Compared with group R, the MWT was significantly increased, and TWL was prolonged at T1-T3, the expression of spinal 3-NT and nitrated MnSOD was down-regulated, and MnSOD activity was increased in group R+ H. Conclusion Spinal peroxynitrite is involved in the mechanism underlying remifentanil-induced hyperalgesia through inhibiting the activity of MnSOD in rats. Key words: Piperidines; Hyperalgesia; Peroxynitrite; Spinal cord