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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。
Tissue releases 5-hydroxytryptamine (5-HT) during inflammation, which plays an important role in the production of inflammatory hyperalgesia. However, the significance of 5-HT2A receptors in inflammatory tissues is not yet clear. This article aims to investigate the role of peripheral 5-HT2A receptors in chronic inflammatory pain. The rats were injected with complete Freund’s adjuvant (CFA) in the posterior plantar and ketotrin, a selective 5-HT2A receptor blocker, at local inflammatory sites. After the foot was treated with heat and mechanical Stimulated withdrawal foot reflex, and immunohistochemistry was used to detect the expression of neuropeptide Y (NPY) in spinal dorsal horn and dorsal root ganglion (DRG). The results showed that administration of ketose (20, 40, and 80μg) topically to inflammation can dose-dependently inhibit CFA-induced thermal hyperalgesia; daily administration of 80μg ketanserin resulted in complete reversal of thermal hyperalgesia by CFA on the third day , And partially reduce tactile hypersensitivity. CFA induced an increase of NPY expression in I ~ II layers of spinal dorsal horn. Ketanin could inhibit the expression of NPY in spinal dorsal horn, but did not change the expression of NPY in DRG. These results indicate that the activation of 5-HT2A receptor in peripheral inflammatory tissues is involved in the occurrence of chronic hyperalgesia. Blocking the 5-HT2A receptor at the inflammatory site can relieve the pain and correct the abnormal changes of dorsal horn cells in spinal dorsal horn which are closely related to pathological pain. Therefore, the peripheral 5-HT2A receptor is expected to become a drug target for treatment of patients with chronic inflammatory hyperalgesia and no central nervous system side effects.