Wei Lai, Zhu Yuan-Mei, Zhang Yu-Xiang, Liang Feng, Jia Hong, Qu Chao-Ling, Wang Jing, Tang Jing-Shi, Lu She-Min, Huo Fu-Quan, Yan Chun-Xia
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Division of Forensic Medicine, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, China.
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Neurochem Int. 2016 Oct;99:85-93. doi: 10.1016/j.neuint.2016.06.006. Epub 2016 Jun 11.
Recent studies have demonstrated that noradrenaline acting in the ventrolateral orbital cortex (VLO) can potentially reduce allodynia induced by spared nerve injury (SNI), and this effect is mediated by α2 adrenoceptor. The present study examined the effect of the α1 adrenoceptors in the VLO on allodynia induced by SNI in the rats. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of selective α1 adrenoceptor agonist methoxamine (20, 50, 100 μg in 0.5 μl) into the VLO, contralateral to the site of nerve injury, increased PWT in a dose-dependent manner. This effect was antagonized by pre-microinjection of the selective α1 adrenoceptor antagonist benoxathian into the same VLO site, and blocked by electrolytic lesion of the ventrolateral periaqueductal gray (PAG). Furthermore, pre-administration of non-selective glutamate receptor antagonist kynurenic acid, phospholipase C (PLC) inhibitor U73122, and protein kinase C (PKC) inhibitor chelerythrine to the VLO also blocked methoxamine-induced inhibition of allodynia. These results suggest that activation of α1 adrenoceptors in the VLO can potentially reduce allodynia induced by SNI. This effect may be direct excitation of the VLO neurons, via PLC-PKC signaling pathway, projecting to the PAG or facilitating glutamate release and then indirectly exciting the VLO output neurons projecting to the PAG, leading to activation of the PAG-brainstem descending inhibitory system which depresses the nociceptive transmission at the spinal cord level.
最近的研究表明，作用于腹外侧眶额皮质（VLO）的去甲肾上腺素可能会减轻由 spared 神经损伤（SNI）诱导的异常性疼痛，并且这种作用是由α2肾上腺素能受体介导的。本研究检测了VLO中α1肾上腺素能受体对大鼠SNI诱导的异常性疼痛的影响。使用von-Frey细丝测量机械性缩爪阈值（PWT）。将选择性α1肾上腺素能受体激动剂甲氧明（20、50、100μg于0.5μl中）微量注射到与神经损伤部位对侧的VLO中，PWT以剂量依赖性方式增加。这种作用被预先将选择性α1肾上腺素能受体拮抗剂贝诺沙噻嗪微量注射到相同的VLO部位所拮抗，并被腹外侧导水管周围灰质（PAG）的电解损伤所阻断。此外，预先向VLO给予非选择性谷氨酸受体拮抗剂犬尿喹啉酸、磷脂酶C（PLC）抑制剂U73122和蛋白激酶C（PKC）抑制剂白屈菜红碱也阻断了甲氧明诱导的异常性疼痛抑制。这些结果表明，VLO中α1肾上腺素能受体的激活可能会减轻SNI诱导的异常性疼痛。这种作用可能是通过PLC-PKC信号通路直接兴奋投射到PAG的VLO神经元，或促进谷氨酸释放，然后间接兴奋投射到PAG的VLO输出神经元，导致PAG-脑干下行抑制系统的激活，从而抑制脊髓水平的伤害性传入。
