阻断炎症部位5-HT2A受体对大鼠完全弗氏佐剂诱发炎性痛和脊髓背角神经肽Y表达的作用

发布时间：2018-10-31 15:30

【摘要】：炎症时组织释放5-羟色胺(5-hydroxytryptamine,5-HT),对炎性痛觉过敏的产生起重要作用。但炎症组织5-HT2A受体在其中的意义尚不明确。本文旨在研究外周组织5-HT2A受体在慢性炎性痛中的作用。大鼠后足底注射完全弗氏佐剂(complete Freund’s adjuvant,CFA),在局部炎性部位给予选择性5-HT2A受体阻断剂酮色林,用行为学检测后足底对热和机械刺激的撤足反射,用免疫组织化学方法检查脊髓背角和背根神经节(dorsal root ganglion,DRG)中神经肽Y(neuropeptide Y,NPY)表达变化。结果显示,炎症局部给予酮色林(20、40、80μg)能剂量依赖性地抑制CFA诱发的热痛觉过敏;每日给予80μg酮色林,在第三天即完全翻转CFA引起的热痛觉过敏,以及部分地减轻触觉超敏。CFA诱发脊髓背角I~II层NPY表达增加,炎症组织局部注射酮色林能抑制脊髓背角NPY的表达增加,但不改变DRG中NPY的表达。这些结果表明:外周炎症组织5-HT2A受体激活参与慢性痛觉过敏的发生;阻断炎症部位5-HT2A受体能缓解疼痛,矫正与病理疼痛密切关联的脊髓背角细胞异常改变。因此,外周5-HT2A受体,有望成为治疗慢性炎性痛觉敏感性增高、不产生中枢神经系统副作用的药物靶点。
[Abstract]:The release of 5-hydroxytryptamine (5-HT) from inflammatory tissues plays an important role in the production of inflammatory hyperalgesia. However, the significance of 5-HT2A receptor in inflammatory tissue remains unclear. The purpose of this study was to study the role of peripheral 5-HT2A receptor in chronic inflammatory pain. Rats were injected with complete Freund's adjuvant (complete Freund's adjuvant,CFA) into the posterior plantar and were given selective 5-HT2A receptor blocker ketoserin at the local inflammatory site. The foot withdrawal reflex of the posterior plantar to heat and mechanical stimulation was detected by behavior. The expression of neuropeptide Y (NPY) in spinal dorsal horn and dorsal root ganglion (dorsal root ganglion,DRG) was detected by immunohistochemical method. The results showed that local administration of ketoserin (20 ~ 4080 渭 g) could inhibit the thermal hyperalgesia induced by CFA in a dose-dependent manner. On the third day, 80 渭 g ketoserin was given to the patients with hyperthermia induced by complete reversal of CFA, and the increase of NPY expression in the I~II layer induced by tactile hypersensitivity and CFA was partly alleviated. Local injection of ketoserin in inflammatory tissues inhibited the expression of NPY in spinal dorsal horn, but did not change the expression of NPY in DRG. These results suggest that the activation of 5-HT2A receptors in peripheral inflammatory tissues is involved in the development of chronic hyperalgesia and that blocking 5-HT2A receptors in inflammatory sites can relieve pain and correct abnormal changes of spinal dorsal horn cells closely associated with pathological pain. Therefore, peripheral 5-HT2A receptor is expected to be a drug target for the treatment of chronic inflammatory pain with increased sensitivity and no side effects in the central nervous system.
【作者单位】：福建师范大学生命科学学院福建省发育和神经生物学重点实验室;
【基金】：supported by the National Natural Science Foundation of China(No.31171072)
【分类号】：R595.3

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