Role of spinal histone acetylation in persistent postoperative pain in rats

Abstract

Objective To evaluate the role of spinal histone acetylation in persistent postoperative pain in rats. Methods Pathogen-free healthy male Sprague-Dawley rats, weighing 200-250 g, aged 2 months, in which intrathecal catheters were implanted at the lumbar level according to an improved method, were used in the study.Eighty-four rats, in which intrathecal catheters were successfully implanted, were divided into Ⅰ-Ⅵ groups(n=14 each)using a random number table.Artificial cerebrospinal fluid 20 μl was intrathecally administered at 1, 2, 3 and 4 days before operation and 1 day after operation inⅠand Ⅳ groups.At 1, 2, 3 and 4 days before operation and 1 day after operation, dimethyl sulfoxide 10 μl and SAHA(50 μg/10μl)were intrathecally injected in Ⅱ and Ⅴ groups and in Ⅲ andⅥ groups, respectively, followed by artificial cerebrospinal fluid(10 μl)flush after each injection.Rats underwent sham operation inⅠ-Ⅲ groups.Persistent postoperative pain was evoked by skin/muscle incision and traction in Ⅳ-Ⅵ groups.The mechanical paw withdrawal threshold(MWT)was measured at 1 day before operation(T0)and 1, 3, 7, 14 and 21 days after operation(T1-5). Four rats were sacrificed in each group after measurement of MWT at T4, and the lumbar segments(L4-6)of the spinal cord were removed for determination of the expression of acetylated histone H3(Ac-H3)and Ac-H4 by Western blot. Results There was no significant difference in each index amongⅠ-Ⅲ groups(P>0.05). Compared with group Ⅰ, the MWT was significantly decreased at T2-5, and the expression of Ac-H3 and Ac-H4 was down-regulated at T4 in group Ⅳ(P<0.05). Compared with group Ⅳ, the MWT was significantly increased at T2-5, and the expression of Ac-H3 and Ac-H4 was up-regulated at T4 in group Ⅵ(P<0.05). Conclusion Histone acetylation is involved in the development and maintenance of persistent postoperative pain in rats. Key words: Histones; Acetylation; Pain, postoperative; Spinal cord