K252a relieved the persistent and postoperative pain through downregulating K +-Cl- cotransporter 2 in the dorsal horn of spinal cord in rats

Abstract

Objective To observe the effects of intrathecal injections of tyrosine kinase receptor B(TrkB) inhibitor K252a on K+-Cl- cotransporter 2(KCC2) expression in the skin/muscle incision and retraction(SMIR)-induced persistent postoperative pain in rats. Methods Fifty two adult male SD rats were randomly and equally divided into four groups, namely the sham group(control group), SMIR group, SMIR+dimethyl sulfoxide(DMSO) group and SMIR+K252a group. Mechanical withdrawal threshold(MWT) was measured at the preoperative day 1 and postoperative days 3, 7, 12, 22 and 32, and KCC2 expression in the spinal dorsal horn was detected at postoperative day 7 by western blot. Results Compared with sham group, the MWT decreased significantly at postoperative days 7, 12, 22 in SMIR group[(22.5 ± 2.3), (24.9 ± 1.4), (29.5 ± 2.4) g] and SMIR+ DMSO group[(24.0 ± 1.9), (24.8 ± 2.3), (26.7 ± 2.1) g] (P 0.05). Compared with SMIR group, KCC2 expression in the spinal dorsal horn in SMIR+K252a group upregulated significantly (P<0.05). Conclusions KCC2 variations in the spinal dorsal horn may participate in the modulation of persistent postoperative pain evoked by SMIR in rats. Key words: Skin/muscle retraction; Persistent postoperative pain; Brain derived neurophic factor; Tyrosine kinase receptor B; K+-Cl- cotransporter 2