Intrathecal injection of dexmedetomidine reduces neuropathic pain in rat model of chronic constriction injury / 中国医师杂志

ABSTRACT

Objective To investigate the effect of intrathecal injection (IT) of dexmedetomidine targeting Toll-like receptor 3 (TLR3) on neuropathic pain and spinal cord levels of TLR3 mRNA,interleukin-1β(IL-1β),tumor necrosis factor-alpha (TNF-α) proteins in rat model of chronic constriction injury (CCI).Methods Male Sprague-Dawley rats were randomly divided into five groups(n =10)the sham group(intrathecal normal saline,IT NS),CCI group (CCI + IT NS),DEX-pre group (CCI + IT DEX pre 2ds),DEX-post group (CCl + IT DEX post 7ds) and DEX + ATIP group (CCI + IT DEX + ATIP).The lumbar intrathecal catheters were implanted in L5_6 of rats and CCI models were established as previously described.The thermal and mechanical nociceptive thresholds were assessed by paw withdrawal latency(PWL) to radiant heat and yon Frey filaments.The DEX was administered intrathecally for 7 days starting from 2 day before surgery or 7day after surgery.The spinal cord expression of TLR3 mRNA was assessed by real-time polymerase chain reaction (PCR).Levels of IL-1β,TNF-α in spinal cord were detected by enzyme-linked immunosorbent assay (ELISA).Results Compared with the sham group,animals in CCI group had significandy lower mechanical (F =12.73,P ＜ 0.05) and thermal pain thresholds (F =14.65,P ＜ 0.05),higher expression of TLR3 mRNA (F =11.03,P ＜ 0.05) and levels of IL-1 β (F =9.67,P ＜ 0.05),TNF-α(F =8.78,P ＜ 0.05) in the spinal cord (P ＜ 0.05).Rats in DEX-pre group had significantly higher mechanical (F =11.03,P ＜ 0.05) and thermal pain thresholds (F =15.03,P ＜ 0.05) and significantly lower expression of TLR3 mRNA (F =14.65,P ＜0.05) and levels of IL-1β (F =12.51,P＜0.05,TNF-α (F =9.01,P ＜0.05) in the spinal cord compared with those in the CCI group (at any observed time points after ligation,but most significantly at 7 d).And the effects of DEX-pre group were abated by IT ATIP at the same time or 7days after surgery alone (P ＜ 0.05).Conclusions Intrathecal injection of DEX can decrease the levels of inflammatory factors by decreasing the TLR3 mRNA in the spinal cord of rats and prophylactic relieve the neuropathic pain induced by CCI.