Mechanism Research Of Intrathecal Injection T0901317 Relieves CCI-induced Neuropathic Pain

Objective:Discusses neuroinflammation and glial cells involved in the occurrence,maintain and mechanism of neuropathic pain.Activated glial cells can produce a variety of inflammatory factors.At the same time,inflammatory factors can further promote glial cell proliferation and activation,which forms a pathological vicious circle.Liver x receptors are ligand-activated nuclear transcription factors,which have significant anti-inflammatory effects.Whether liver x receptor activation can inhibit neuroinflammation and glial cell activation,thereby reducing neuropathic pain are not clear.The aim of this study was to investigate the effect of intrathecal injection of liver x receptor agonist T0901317 on glial cell activation,inflammatory factor expression and neuropathic pain induced by sciatic nerve ligation.Methods:The model of neuropathic pain was established by ligating the sciatic nerve of rats.From the day of surgery to the third day,150 μg/kg T0901317 was given once a day.Thermal withdrawl latency(TWL)and mechanical withdrawl threshold(MWT)were observed at different time points in rats to evaluate the effect of liver x receptor activation on neuropathic pain.Reverse transcriptase and western blot were used to detect the expression of GFAP,IBA-1,IL-6 and TNF-a genes and proteins in rat dorsal horn,by which to evaluate the effect of liver x receptor activation on glial cell activation and neuroinflammation in spinal dorsal horn.Results:Compared with the sham group,the TWL and MWT were significantly decreased in the chronic sciatic nerve injury group(CCI group)on the 4th day after operation,and reached the lowest value on the 7th day.(P<0.05).With intrathecal administration of T0901317,TWL and MWT were significantly higher in the 7th-14th day than in the CCI group(P<0.05).In sham group,The levels of GFAP,IBA-1,IL-6 and IL-6 in the dorsal horn of the spinal cord were significantly lower than those in the CCI group,and the difference was statistically significant.In contrast,intrathecal administration of T0901317 significantly reduced the expression of GFAP,IBA-1,IL-6 and TNF-α in CCI-induced spinal dorsal horn.Conclusion:Intrathecal injection of liver x receptor agonist T0901317 can relieve neuropathic pain induced by sciatic nerve ligation.The mechanism may be related to T0901317-induced inhibition of spinal dorsal horn glial cell activation and expression of inflammatory factors.