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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
  • ISSN号:0371-0874
  • 期刊名称:《生理学报》
  • 时间:0
  • 分类:Q426[生物学—神经生物学;生物学—生理学] R338.3[医药卫生—人体生理学;医药卫生—基础医学]
  • 作者机构:[1]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,福州350108
  • 相关基金:This work was supported by the National Natural Science Foundation of China (No. 31171072).
中文摘要:

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受体在眵十牛炎性痛中的作用。大鼠后厅底注射完全弗氏佐剂(com—pleteFreund’Sadjuvant,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(dorsalrootganglion,DRG)中神经肽Y(neuropeptideYNPY)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。

英文摘要:

5-bydroxytryptamine (5-HT) released in inflammatory tissues plays a pivotal role in pain hypersensitivity. However, it is not clear whether 5-HT2A receptors in the inflamed tissues mediate this effect. The present study investigated the contribution of 5-HT2A receptors in the periphery to chronic inflammatory pain. Complete Freund's adjuvant (CFA) was injected subcutaneously in the hind- paw of rats. The selective 5-HT2A receptor antagonist ketanserin was given in the inflamed site. Paw withdrawal latency respond- ing to heat or mechanical stimuli was measured. Expression of neuropeptide Y (NPY) in the spinal dorsal horn and dorsal root ganglia (DRG) was assayed using immunohistochemistry technique. The results showed that ketanserin administered in the inflamed site inhibited thermal hyperalgesia in a dose-dependent manner (20, 40 and 80 μg) induced by the intraplantar injection of CFA. Ketanse- fin given once per day at a dose of 80 μg abolished heat hyperalgesia and also attenuated mechanical allodynia on the third day. CFA injection increased the expression of NPY in superficial laminae of the spinal cord, but not in the DRG. The local treatment of ketanserin completely inhibited CFA-induced increase in NPY expression in superficial laminae of the spinal cord. These results indicated that activation of 5-HT2A receptors in the inflamed tissues was involved in the pathogenesis of inflammatory pain and the blockade of 5-HT2A receptors in the periphery could relieve pain hypersensitivity and normalize the cellular disorder in the spinal dorsal horn associated with pathological pain. The present study suggests that the peripheral 5-HT2A receptors can be a promising target for pharmaceutical therapy to treat chronic inflammatory pain without central nervous system side effects.

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期刊信息
  • 《生理学报》
  • 中国科技核心期刊
  • 主管单位:中国科学院
  • 主办单位:中国生理学会 中国科学院上海生理研究所
  • 主编:王建军
  • 地址:上海岳阳路319号31B楼
  • 邮编:200031
  • 邮箱:actaps@sibs.ac.cn
  • 电话:021-54922832
  • 国际标准刊号:ISSN:0371-0874
  • 国内统一刊号:ISSN:31-1352/Q
  • 邮发代号:4-157
  • 获奖情况:
  • 中国自然科学核心期刊,中国科学院优秀期刊特别奖,荣获首届国家期刊奖
  • 国内外数据库收录:
  • 美国化学文摘(网络版),波兰哥白尼索引,荷兰文摘与引文数据库,美国生物医学检索系统,美国生物科学数据库,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:8098