Increase in hemokinin-1 mRNA in the spinal cord during the early phase of a neuropathic pain state
Increase in hemokinin-1 mRNA in the spinal cord during the early phase of a neuropathic pain state
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DOI：
10.1038/bjp.2008.301
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发表时间：
2008-11-01
影响因子：
7.3
通讯作者：
Suzuki, H.
中科院分区：
文献类型：
--
作者：
Matsumura, T.;Sakai, A.;Suzuki, H.
背景和目的：P物质（SP）是速激肽家族的代表性成员，在生理和病理条件下参与伤害感受。最近，hemokinin-1（HK-1）被鉴定为该家族的新成员。尽管HK-1作用于被认为是SP先天性的NK 1速激肽受体，但HK-1在神经病理性疼痛中的作用仍然未知。利用大鼠坐骨神经慢性压迫性损伤（CCI）作为神经病理性疼痛模型，我们检测了SP和HK-1编码基因表达的变化，（分别为TAC 1和TAC 4）在L4/L5脊髓和L4/L5背根神经节（DRG）中与这种神经病理性疼痛状态下疼痛相关行为的变化相关的TAC 4 mRNA水平在CCI后第3天在脊髓背侧的同侧增加，但在DRG中没有。与此相反，TAC 1 mRNA水平显着增加，在背根神经节在CCI后3天没有任何变化的背侧脊髓。对培养的小胶质细胞系的分析揭示了小胶质细胞中TAC 4 mRNA的存在。米诺环素，小胶质细胞活化的抑制剂，阻断CCI后增加的TAC 4 mRNA的表达，并抑制相关的疼痛相关的行为和小胶质细胞活化在spinalcord.Conclusions和影响：目前的结果表明，HK-1的表达增加至少部分在激活的小胶质细胞神经损伤后，显然是参与神经病理性疼痛的早期阶段。
Background and purpose: Substance P (SP), a representative member of the tachykinin family, is involved in nociception under physiological and pathological conditions. Recently, hemokinin-1 (HK-1) was identified as a new member of this family. Although HK-1 acts on NK1 tachykinin receptors that are thought to be innate for SP, the roles of HK-1 in neuropathic pain are still unknown.Experimental approach: Using rats that had been subjected to chronic constrictive injury (CCI) of the sciatic nerve as a neuropathic pain model, we examined the changes in expression of SP- and HK-1-encoding genes (TAC1 and TAC4, respectively) in the L4/L5 spinal cord and L4/L5 dorsal root ganglia (DRGs) in association with changes in pain-related behaviours in this neuropathic pain state.Key results: The TAC4 mRNA level was increased on the ipsilateral side of the dorsal spinal cord, but not in DRGs, at day 3 after CCI. In contrast, the TAC1 mRNA level was significantly increased in the DRGs at day 3 after CCI without any changes in the dorsal spinal cord. Analysis of a cultured microglial cell line revealed the presence of TAC4 mRNA in microglial cells. Minocycline, an inhibitor of microglial activation, blocked the increased expression of TAC4 mRNA after CCI and inhibited the associated pain-related behaviours and microglial activation in the spinal cord.Conclusions and implications: The present results suggest that HK-1 expression is increased at least partly in activated microglial cells after nerve injury and is clearly involved in the early phase of neuropathic pain.