The Mechanism Of IL-21 And IL-21R In Neuropathic Pain In Rat Red Nucleus

BackgroundRed necleus(RN) is a very important part in the extrapyramidal system,plays a key role in the control of movement,generally,red nucleus mainly regulate muscle tension and flexor reflex,However,recent studies have shown that RN has a moderating effect on somatic pain,molecules and cells in the immune system play a key role in the pain mechanism.Therefore,the red nucleus is involved in the regulation of pain and promotes or inhibits the action of different neurotransmitters and cytokines.ObjectiveTo study the mechanism of IL-21 and IL-21 R in neuropathic pain induced by SNI rat model.MethodsExperiments were performed with 48 SD rats(Sprague-Dawley)with weight of200-230 g.The rats were divided into three groups: control group,sham operation group and SNI model group,each group included 16 rats which further was divided into treatment group and non-treatment group which containd 8 rats respectively.After a week when SNI modeling was finished,the non-treatment group rats were killed in the control group,sham operation group and SNI model group.The total RNA and total protein of red nucleus were extracted,and the levels of IL-21 and IL-21 R in the red nucleus were detected,as well as expression of NF-?B,MAPK,ERK and JNK protein expression in the red nucleus.At the same time in a week after SNI,the stainless steel casing guided stereotactic implantation left RN of treatment group rats,and stainless steel plug is inserted into the guide cannula and kept in place,one week after catheter insertion(the secondweeks after SNI modeling),the antibody(500 ng)of IL-21 was administered using a microinjector with a tip extending beyond the catheter tip of 2.0 mm.At the end of the experiment,the toluidine blue dye was injected into the RN and the microinjection sites were histologically validated.And then,the protein expression of NF-?B,MAPK,ERK and JNK were tested in each groups.ResultsThis study successfully established a model of neuropathic pain with unilateral mechanical abnormalities.Compared with the control group and sham operation group,the expression of IL-21 and IL-21 R and NF-?B,MAPK,ERK and JNK were significantly increased in RT-PCR and Western blot experiments.The expression of NF-?B,MAPK,ERK and JNK protein in the red nucleus of SNI rats were significantly decreased after IL-21 signal was blocked by IL-21 antibody in the red nucleus of rats.ConclusionIn the SNI neuropathic pain model,IL-21 and IL-21 R play a role together in neuropathic pain;IL-21 and IL-21 R make immune response for neuropathic pain through NF-?B,MAPK,ERK and JNK signaling pathways.