The Research On Analgesic Effect Of Matrine And Its Mechanism Involved In Ras/Raf/ERK1/2 Signaling Pathway On Vincristine-induced Neuropathic Pain In Mice

Objective In this study we investigated anti-nociceptive effects of matrine(MT)through inhibition of Ras/Raf/ERK1/2 signaling pathwayin neuropathic pain model induced by vincristine(VCR).Methods The anti-nociceptive effects of the MT were assessed inmechanical allodynia,thermal hyperalgesia,cold allodynia and mechanicalhyperalgesiatests.Electrophysiological testwas used to evaluate the functional change of sciatic nerve.Histopathological impairment was estimated by performing hematoxylin and eosin(HE)staining in sciatic nerve and spinal cord tissues.Moreover,the expressions of GFAP and p-ERK1/2 immuno-staining intensitywereassessed byimmunofluorescence.Besides,the expression of Ras,c-Raf,p-c-Raf,ERK1/2,p-ERK1/2,TNF-?,IL-6 and IL-10 protein were assessed by western blot in spinal cord.In addition,q PCR was used to quantify the m RNA level of Ras,c-Raf,ERK1/2 in spinal cord tissues.Results The MT(60mg/kg)could increase the paw withdrawal threshold in the mechanical allodynia test(p<0.01),extended the paw withdrawal latency in the thermal hyperalgesia test significantly(p<0.01),increase the paw pressure in the mechanical hyperalgesia test(p<0.01)and MT(60 and 30mg/kg)decreased the paw lifts in the cold allodynia test(p<0.01).The MT(60 and30mg/kg)could increase sensory nerve conduction velocity(SNCV)and sensory nerve action potential(SNAP)amplitude(p<0.01).After administration of MT(60mg/kg)treatment,nerve fibers and axons cellswere restored to some extent in the sciatic nerve,spinal dorsal horn and dorsal root ganglion.Treatment with MT(60mg/kg)decreased the expressions of GFAP and p-ERK1/2 immuno-staining intensity,Ras,p-c-Raf,p-ERK1/2,IL-6,TNF-?protein and Ras,c-Raf,ERK1/2 m RNA level,augmented the expression of IL-10 protein(p<0.01).Conclusions MT had antinociceptive effects through regulation of Ras/Raf/ERK1/2 signaling pathwayon neuropathic pain model induced by VCR.