Effect of intrathecal administration of a mixture of butorphanol and ketamine on cAMP-PKA-CREB signal transduction pathway in spinal dorsal horn of rats with inflammatory pain

Abstract

Objective To investigate the effect of intrathecal administration of a mixture of butorphanol and ketamine on cAMP-PKA-CREB signal transductian pathway in the spinal dorsal ham of the rats with inflammatory pain. Methods Twenty-four male SD rats, weighing 240-280 g,in which intrathecal catheters were successfully placed, were divided into 4 groups randomly (n = 6 each): inflammatory pain group (group IP), butorphanol group (group B), ketamine group (group K), and butorphanol + ketamine group (group BK). The inflammatory pain was induced by injection of 5% formalin 50 μl into the plantar surface of left hind paw. Normal saline 10 μl, butorphannl 12.5 μg, ketamine 50 μg, and a mixture of butorphanol 12.5 μg and ketamine 50 μg was injected intrathecally 30 min before subcutaneous injection of formalin in group IP, B, K and BK respectively.Pain intensity score (PIS) was used to assess pain behavior every 5 min within an hour after subcutaneous injection of formalin. The animals were killed at 2 h after subcutaneous injection of formalin, and the L5 segment of the spinal cord was removed for determination of protein kinase A (PKA) and phosphorylated cAMP response element binding protein (p-CREB) expression using immunohistochemistry. Results Fonnahn administration induced pain behaviour expressed as two phases. PIS scores, PKA and p-CBEB expression, and staining scores were significantly lower during the fast and second phases in group BK than in group IP (P 0.05). Conclusion lntrathecal injection of a mixture of butorphanol and ketamine can reduce inflammatory pain in rats, and the mechanism may be related to the cAMP-PKA-CREB signal transduction pathway. Key words: Butorphanol; Ketamine; Cyclic AMP; Cyclic AMP-dependent protein kinnses; Cyclic AMP response element-binding protein; Pain; Injections, spinal