Role of phosphatidylinositol 3-kinase/protein-serine-threonine kinases signal transduction pathway in EphB receptor-mediated neuropathic pain in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of phosphatidylinositol 3-kinase (PI3K)/protein-serine-threonine kinases(Akt) signal transduction pathway in EphB receptor-mediated neuropathic pain in rats.Methods Forty-eight pathogen-free male SD rats aged 2-3 months weighing 150-180 g were randomly divided into 6 groups (n =8 each)groups sham operation (groups S1 and S2 ); groups chronic constrictive injury (CCI) (groups C1and C2 ) and groups EphBI-Fc (EphB receptor antagonist) + CCI (groups E1 and E2 ).Neuropathic pain was induced by placing 4 ligatures on left sciatic nerve at 1 mm intervals with 5-0 silk thread in groups C1,C2,E1 and E2.EphBI-Fc 0.5 μg in 5 μl normal saline was injected intrathecally 1 h before operation and at 1 and 2 d after operation (group E1 ) or on 5th day after operation (group E2).Normal saline 5 μl was injected intrathecally instead of EphBI-Fc 1 h before operation and at 1 and 2 days after operation (groups S1 and C1 ) or on 5th day after operation (groups S2 and C2 ).Pain withdrawal latency to noxious thermal stimulation (PWL) and pain withdrawal threshold to noxious mechanical stimulation (PWT) were measured before operation and at 1,3 and 5 d after operation.The animals were sacrificed at 5 d after operation after measurement of pain threshold.The lumbar segment of spinal cord (L4-6) was removed for determination of c-Fos,PI3K and phosphorylated Akt(p-Akt) expression.Results CCI significantly reduced PWL and PWT and up-regulated spinal c-Fos,PI3K and p-Akt expression in groups C1 and C2 as compared with groups S1 and S2.EphB1-Fc significantly decreased hyperalgesia and the upregulated spinal Fos,PI3K and p-Akt protein expression induced by CCI in groups E1 and E2 as compared with groups C1 and C2.Conclusion Spinal EphB receptor is involved in the development and maintenance of neuropathic pain through PI3K/Akt signal transduction pathway.