Effect of intrathecal minocycline on the expression of spinal GRK2 in rats model with persistent postoperative pain

Objective To investigate the effects of intrathecal minocycline (a selective inhibitor of microglial activation) on the expression of spinal G protein-coupled receptor kinase 2 (GRK2) in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR). Methods Forty male SD rats implanted intrathecal catheter were randomly divided into 4 groups (n=10 each) : Sham + intrathecal saline group (group Ⅰ), Sham + intrathecal minocycline group (group Ⅱ), SMIR + intrathecal saline group (group Ⅲ), SMIR + intrathecal minocycline group (group Ⅳ). Normal saline 20 μl was intrathecally administered at 30 min before the operation and 1, 2 and 3 days after the operation in groupⅠ and Ⅲ. At 30 min before the operation and 1, 2 and 3 days after the operation, minocycline (100 μg/10μl) was intrathecally injected in group Ⅱ and Ⅳ, followed by normal saline 10 μl flushed after each injection. Rats underwent sham operation in group Ⅰand Ⅱ. Persistent postoperative pain was evoked by skin/muscle incision and traction method in group Ⅲ and Ⅳ. A PE-10 catheter was inserted into the intrathecal space according to the method described by Yaksh. The mechanical paw withdrawal threshold (MWT) was measured at 1 day before the operation and 3, 7, 14 and 21 days after the operation. Four rats were sacrificed in each group after measurement of MWT at 14 day after the operation, and the lumbar segment (L4-6) of the spinal cord were removed for determination of the expression of GRK2 by Western blot. Results There was no significant difference in MWT and the expression of spinal GRK2 in groupⅠ and Ⅱ (P>0.05). Compared with groupⅠ, the MWT was significantly decreased at 3, 7, 14 and 21 days after the operation, and the expression of spinal GRK2 was significantly down-regulated at 14 day after the operation in group Ⅲ (P<0.05). Compared with group Ⅲ, the MWT was significantly increased at 3, 7, 14 and 21 days after the operation, and the expression of spinal GRK2 was significantly up-regulated at 14 day after the operation in group Ⅳ (P<0.05). Conclusion The activation of microglia may be related to down-regulated expression of spinal GRK2 in a rat model with persistent postoperative pain evoked by SMIR. Key words: Spinal cord; Minocycline; G protein-coupled receptor kinase 2; Microglia; Pain, postoperative; Analgesia