Establishment of postoperative sustained injury sensitization model of inflammatory pain-sensitivity

Abstract

Objective To investigate the effects of spinal PKMζ on the maintenance of persistent nociceptive sensitization after plantar incision following peripheral inflammation in rats, adapting a modified hyperalgesia priming model that produces a state of sensitization closely resembling clinical situations with increased risk of development of persistent postoperative pain. Methods Twenty-eight healthy adult male Sprague-Dawley rats weighing 220-250 gram were randomly divided into two groups (n=14): NS+Surgery group which was induced by intraplantar injection of carrageenan (1%, 5 μl), and Car.+Surgery group with NS (0.9%NaCl, 5 μl) into one hindpaw in rats. Changes of pain behavior were assessed by withdrawal threshold to von Frey filament stimulation intensity, response latency of the hindpaw to radiant the thermal and a cumulative pain scores 1-6 d before incision as well as 1-10 d after incision. The expression of PKMζ was measured in the spinal cord by Western blotting and immunohistochemical analysis at 1, 3, 10 d after incision. Results There were no significant differences in the value of MWT and TWL before treatment and surgery. Compared with NS+ Surgery group, the MWT and TWL of Car.+Surgery group decreased significantly (P<0.05), which lasted about 3 d and returned to normal. All rats showed allodynia in response to innocuous mechanical stimulation. Compared with pre-incision, the MWT and TWL of two groups decreased significantly (P<0.05). While the MWT and TWL of NS+Surgery group increased thereafter and returned to normal by 6 d. Compared with pre-incision and NS+Surgery group, the MWT and TWL of Car.+Surgery group decreased significantly, lasting for 10 d (P<0.05). Compared with NS+Surgery group, the number of positive cells and the expression of spinal PKMζ after incision remarkably increased in Car.+Surgery group (P<0.05). Conclusion Spinal PKMζ involves in the development and maintenance of persistent nociceptive sensitization after plantar incision following peripheral inflammation pain in rats. Key words: Protein kinases; Spinal cord; Models, animal; Persistent nociceptive sensitization