Effects of intrathecal injection Roscovitine on the pain behavior and the expression of ERK1/2 and PPARγ protein in spinal cord in rats with neuropathic pain

Abstract

Objective To investigate the effects of intrathecal injection of Roscovitine on the pain behavior and the expression of pERK1/2 and pPPARγ receptor in spinal cord in rats with neuropathic pain. Methods Fifty-two male adult Sprague-Dawley rats of 220~250 g were randomly divided into 4 groups: Sham+ DMSO group (dimethyl sulfoxide, S+ D group), Sham+ Roscovitine (S+ R) group, CCI+ DMSO group (I+ D), CCI+ Roscovitine (I+ R) group. The corresponding drugs were administered by intrathecal injection from the seventh day after CCI once a day for 14 days. The right hind paw mechanical threshold value(PMWT) was measured by Von Frey filament and paw thermal withdrawal latency(PWTL) was measured by Hargreaves methods before 1 day and 3 d, 7 d, 10 d , 14 d after surgery. The spinal cord lumbar enlargement was taken at 14 d after surgery, and Cdk5, p35, phosphorylated ERK protein(pERK), total ERK protein(ERK), phosphorylated PPARγ protein (pPPARγ) and total PPARγ protein (PPARγ) were detecteded by Western blot. Results Roscovitine was administered by intrathecal injection alleviated mechanical allodynia and thermal hyperalgesia of CCI rats.Compared with I+ D group, PWMT in I+ R group at 7 d, 10 d, 14 d after administration((4.65±0.08)g, ( 6.47±0.12)g, ( 7.90±0.19)g, ) vs ((3.71±0.06)g, (2.45±0.17)g, ( 2.31±0.15)g)(Fgroup=505.71, P<0.05, Ftime×group=15.33, P<0.05) , PWTL((9.22±0.33)s, (13.52±0.43)s, (12.63±0.88)s) vs ((8.02±0.20)s, (5.90±0.28)s, (5.40±0.38)s) (Fgroup=355, P<0.05, Ftime×group=8.589, P<0.05) were significantly increased. Compared with I+ D group(p35(0.58±0.02), pERK (1.12±0.13), pPPARγ (0.77±0.16)), p35 (0.46±0.04, F=11.06, P<0.05) and pERK(0.79±0.11, F=22.91, P<0.05) in I+ R group, were significantly dereased, and the expression of pPPARγ(0.99±0.13, F=17.62, P<0.05))was significantly increased. Conclusion Intrathecal injection Roscovitine can alleviate both mechanical allodynia and thermal hyperalgesia in rats with neuropathic pain, and its mechanisms may be related to the inhibition of Cdk5/p35 and ERK activity, enhancement of PPARγ activity in the spinal dorsal horn. Key words: Neuropathic pain; Cyclin-dependent protein kinases 5; Extracellular signal-regulated kinase1/2; Peroxisome proliferator-activated receptor gamma; Spinal dorsal horn