Changes in expression of spinal p-PKMζ during remifentanil-induced hyperalgesia in rats with incisional pain

Abstract

Objective To evaluate the changes in the expression of spinal phosphorylated protein kinase Mζ (p-PKMζ) during remifentanil-induced hyperalgesia in rats with incisional pain. Methods Thirty-two heathy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, were randomly dvided into 4 groups (n= 8 each) using a random number table: control group (group C), remifentanil group (group R), incisional pain group (group I), and incisional pain + remifentanil group (group I+ R). In group R, a catheter was inserted into the caudal vein, and remifentanil was infused for 60 min at a rate of 1 μg·kg-1·min-1 via the catheter.A 1 cm longitudinal incision was made in the plantar surface of the left hindpaw to establish the model of incisional pain in anesthetized rats.In group I, incisional pain was produced, and the normal saline equal to the volume of remifentanil was infused via the catheter.In group I+ R, incisional pain was produced, and remifentanil was infused for 60 min at a rate of 1 μg·kg-1·min-1 via the catheter.While the equal volume of normal saline was given in group C. At 24 h before remifentanil infusion, and 2, 6, 24 and 48 h after the end of remifentanil infusion (T0-4), the mechanical paw withdrawal threshold (MWT) and thermal paw withdraw latency (TWL) were measured.The rats were sacrificed after the last measurement of pain threshold, and the lumbar segments (L4-6) of the spinal cord were removed for determination of the expression of PKMζ and phosphorylated PKMζ (p-PKMζ) by Western blot.The ratio of p-PKMζ/PKMζ was calculated. Results Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T1-4, the expression of PKMζ and p-PKMζ was up-regulated at T4, and the ratio of p-PKMζ/PKMζ was increased in R, I and I+ R groups (P<0.05). Compared with I and R groups, the MWT was significantly decreased, and the TWL was shortened at T1-4, the expression of PKMζ and p-PKMζ was up-regulated at T4, and the ratio of p-PKMζ/PKMζ was increased in group I+ R (P<0.05). Conclusion Up-regulated expression of spinal p-PKMζ is involved in the development of remifentanil-induced hyperalgesia in rats with incisional pain. Key words: Piperidines; Pain, postoperative; Hyperalgesia; Protein kinase C; Spinal cord