Effects of intrathecal H89 on phosphorylation of cAMP element binding protein in the spinal dorsal horn neurons hiduced by chronic constriction injury to sciatic nerve in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of a highly selective protein kinase A (PKA) inhibitor, H89, injected intrathecally (IT) on hyperalgesia and phosphorylation of cAMP element binding protein(pCREB) in the dorsal horn neurons of the spinal cord induced by chronic constriction injury (CCI) to the sciatic nerve.Methods Fifty-eight adult female SD rats weighing 230-270 g were used in this study. CCI was produced by 4 loose ligatures place on the sciatic nerve of right hind leg at 1 mm interspace with 3-0 silk suture. The experiment was carried out in two parts. In part Ⅰ 28 animals were randomized to receive H89 1 (group H1), 2 (group H2 ) or 4 nmol (group H4) or 10 ?l of DMSO (the solvent) 10mmol?L-1 (control group) intrathecally (IT) (n = 7 each) 7 days after surgery. The paw-withdrawal latency following mechanical (MWL) and thermal stimulation (TWL) were recorded before (baseline) and 15, 30 and 60 min after drug administration. In part Ⅱ 24 rats were randomized to receive H89 1, 2 or 4 nmol or 10 ?l of DMSO 10 mmol?L-1 IT as in part Ⅰ (group H1, H2, H4 and control group, n = 6 each) . Another 6 animals received 10 ?l of DMSO 10 mmol?L IT 7 days after sham operation. The animals were killed 30 min after drug administration and lumbar (L4.5) segment of spinal cord was removed for determination of pCREB expression in the dorsal horn neurons of spinal cord using immuno-histochemical technique. Results MWL and TWL were significantly increased after drug administration in group H2(at 15min) and group H4(at 15 and 30 min) as compared to the baseline values(P