Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats
Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats
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DOI：
10.4097/kjae.2014.66.1.52
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发表时间：
2014-01-01
影响因子：
2.9
通讯作者：
Joo, Jin-Deok
中科院分区：
文献类型：
--
作者：
Kwon, So-Young;Yeom, Jae Hwa;Joo, Jin-Deok
背景：脊髓神经结扎产生的神经病鼠显示出更高水平的p38， c-Jun nh2末端激酶和细胞外信号调节激酶p44/42 （ERK 1/2）的分裂原活化蛋白激酶（MAPKs）。本研究的作者旨在了解氯胺酮对p38 MAPK和炎症反应的影响，以及它对神经性疼痛发展的影响。方法：以Sprague-Dawley大鼠为实验对象，采用Chung法制备神经病变大鼠。研究分为假手术组、神经性疼痛加生理盐水组（NP + NS）、神经性疼痛加氯胺酮组（NP + Keta）三组。将生理盐水或氯胺酮通过植入皮下的微渗透泵注入神经病变大鼠体内。一周后，通过western blots和逆转录聚合酶链反应检测和比较phospho-p38、p38 MAPK和促炎细胞因子的数量。结果：与对照组相比，NP + NS组的磷酸化p38、p38 MAPK水平显著升高，促炎因子、肿瘤坏死因子α (TNF α)、细胞间粘附分子1 （ICAM1）水平显著升高。然而，在NP + Keta组中，与NP + NS组相比，phospho-p38、p38 MAPK、TNF α和ICAM1均降低。在NP + Keta组中，足爪戒断阈值测试也显示出机械异常性痛的恢复趋势。结论：在神经性疼痛的发展过程中，p38 MAPK与炎症反应显著相关，氯胺酮的使用降低了p38 MAPK和促炎细胞因子。因此，适当使用氯胺酮可有效预防和治疗周围性损伤后的神经性疼痛。
Background: Neuropathic rats created by spinal nerve ligation are known to show higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases (MAPKs). The authors of this study aimed to understand the effect of ketamine on p38 MAPK and inflammatory responses, as well as its effect on the development of neuropathic pain.Methods: The neuropathic rats were prepared by Chung's method with Sprague-Dawley rats. The research was carried out on three groups, a sham-operated group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine was infused into the neuropathic rats through a mini-osmotic pump implanted in the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction.Results: In comparison to the control group, the NP + NS group showed a significant increase of phospho-p38 and p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor alpha (TNF alpha), and intercellular adhesion molecule 1 (ICAM1). However, in the NP + Keta group, phospho-p38, p38 MAPK and TNF alpha and, ICAM1 were reduced in comparison to the NP + NS group. The paw withdrawal threshold test also showed the trend of recovery from the mechanical allodynia in the NP + Keta group.Conclusions: In the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines. Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.