The Study Of Liver X Receptor Agonists In The Treatment Of Neuropathic Pain

ObjectiveThrough researching the contact between liver X receptors (LXR) agonists and neuropathic pain(NP), and discussing the mechanism of LXR agonists in the treatment of NP, it would provide a theoretical basis for LXR agonists in the treatment of NP, find a new target for the treatment of NP, so as to relieve the pain in patients.Methods1. The mechanical pain threshold measured by the method of up and down, using von Frey Filaments to stimulate the plantar. Behavioral test software was help to transform the measurements into 50% paw withdrawal threshold (50% PWT), which declined meaned a drop of mechanical pain threshold, the same as the increasing of pain degree;2. The operation of spared nerve injury (SNI), and lumbar catheterization in the spinal subarachnoid space had been performed in SD male rats. Meanwhile, 50%PWT had been measured pre and post operation, which can observe the changes in the mechanical pain before and after modeling;3. The rats that SNI modeling and intrathecal catheter had been established successfully were selected for drug experiment, they were randomly divided into control group and experimental group:control group was intrathecal administration of phosphate buffer solution(placebo, the solvent of IL-10 antibody) and LXR agonists, while experimental group was intrathecal injection of IL-10 antibody and LXR agonists.50% PWT valuated the effects of intrathecal administration.4. Three groups, including normal group, SNI group, and the group that had been intrathecal injected of LXR agonists, were selected for Western Blot to observe the changes of NF-κ B/p65, P450scc and IL-10, and Immunofluorescence Histochemistry to observe the expression of P450scc;5. Experimental datas were analyzed by SPSS 20 statistical software.Results1.50%PWT in SNI rats changed not only in the left hind limb (the lesioned limb, P<0.001), but also in the right hind limb (normal limb, P<0.05);2. The pain in left hind limb was relieved by intrathecal administration of LXR agonists on the seventh day after SNI operation. The therapeutical effect occurred in 1 hour after administration (P<0.05),4 hours to the peak (P<0.01), and then gradually decreased. The right hind limb did not cause significant impact;3. Intrathecal injection of IL-10 antibody could reverse the therapeutic effect of LXR agonists on NP in 2 hours after administration (P<0.05).4. The expression of NF-κB/p65 increased, while the expression of nerve steroidal key enzymes P450scc and the anti-inflammatory cytokine IL-10 gradually down after the operation of SNI; P450scc was mainly expressed in neurons;The expression of NF-κB/p65 was down, while IL-10 was up through intrathecal administration of LXR agonists on the seventh day after SNI operation;ConclusionNP has relieved by intrathecal administration of LXR agonists in rats, the mechanism may be related to LXR agonists promote the expression of anti-inflammatory cytokine IL-10. So, the use of LXR agonists may be a novel therapy for NP.