Basic & Clinical Medicine ›› 2015, Vol. 35 ›› Issue (8): 1061-1066.

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Etanercept alleviates lumbar disc herniation-induced hyperalgesia and mRNA expressions of chemokine CCL2/CCR2 in DRG and spinal cord of rats

  

  • Received:2014-06-20 Revised:2015-03-28 Online:2015-08-05 Published:2015-07-15

Abstract: Objective: To observe the effects of tumor necrosis factor-? (TNF-?) inhibitor etanercept on hyperalgesia of rats with lumbar disc herniation, as well as on the expression of chemokine CCL2 and its receptor CCR2 in DRG (dorsal root gangalion) and spinal cord. Methods: SD rats were randomly divided into six groups: Normal group (Control), Sham group (Sham), Nucleus pulposus transplantation Group (NP), NP + Vehicle group (Vehicle), NP + Etanercept 10 ?g (Etanercept 10 ?g), NP + Etanercept 100?g(Etanercept100?g).The mechanical withdrawal threshold (MWT) of the left hind paw of rats in different group was measured at 1 d before and different time points after the surgery. The real-time quantitative PCR was used to measure the mRNA expression level of TNF-α, CCL2/CCR2; Immunohistochemical staining was applied to investigate the expression of ED-1 and ATF3 in DRG. Result (1) Compared with Sham group, MWT in NP group was reduced significantly from1 d after the operation (P < 0.001), and lasted for more than 21 d (P < 0.001); (2) Intrathecal injection of etanercept (100 mg) attenuated the NP-induced mechanical allodynia at 2,3,4 d (P < 0.001); (3) Pretreatment of etanercept (100 mg ) inhibited the up-regulation of CCL2 and CCR2 mRNA in both DRG and spinal cord. Conclusion: Intrathecal injection of etanercept inhibits the neuropathic pain caused by the auto transplantation of nucleus pulposus. The mechanisms may be partly due to the inhibition of CCL2/CCR2 upregulation.

Key words: Keywords: Lumber disc herniation, spinal cord, DRG, TNF-α, CCL2, CCR2