The Study On Analgesic Effect Of Oxymatrine Involved In CaMKII/CREB Signaling On Neuropathic Pain

Purpose In this study we investigated antinociceptive effects of oxymatrine (OMT)through regulation of CaMKII/CREB signaling in a chronic neuropathic pain model inducedby chronic constrictive injury (CCI) of the sciatic nerve.Methods The antinociceptive effects of the OMT were assessed in mechanical allodyniaand cold allodynia tests. Adopting Calcium Chloride Injection (CaCl2), the CAMKII inhibitorKN-93and AIP to investigate the influence on the analgesic effect of OMT and analyze itsanalgesic mechanisms. Total calcium levels were determined after day14to assessbiochemical alterations. Immunofluorescence assay was used to evaluate the expressions ofCaMKII. Western blotting assay was used to evaluate the expressions of tCaMKII, pCaMKII,tCREB and pCREB immuno-staining positive neurons and protein.Results1. The intraperitoneal administration of OMT (160,80mg/kg) could increase thepaw withdrawal threshold in the mechanical allodynia test (P<0.05), ip OMT (160,80,40mg/kg) remarkably decreased the paw lifts in the cold allodynia test (P<0.05).2. Ith KN-93(1.25μg/site), AIP (0.02μg/site) significantly enhanced the analgesiceffect of OMT (35mg/kg)(P<0.01), ith CaCl2(0.5μg/site) significantly antagonized theanalgesic effect of OMT (160mg/kg)(P<0.01).3. Compare to sham group, CCI produced a significant rise in total calciumlevel(P<0.05). Treatment with OMT (80and160mg/kg) attenuated the CCI-induced changesin total calcium level(P<0.05). 4. Intraperitoneal administration of OMT (160mg/kg) decreased the mean IOD ofpCaMKII in the dorsal horn and expression of pCaMKII and pCREB protein (P<0.01).Conclusion OMT can produce antinociceptive effects on a chronic neuropathic painmodel induced by chronic constrictive injury of the sciatic nerve. Regulation ofCaMKII/CREB signaling maybe the targets for the antinociceptive effects of OMT on achronic neuropathic pain model induced by chronic constrictive injury of the sciatic nerve.