• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular pain >Spinal astrocytic activation contributes to both induction and maintenance of pituitary adenylate cyclase-activating polypeptide type 1 receptor-induced long-lasting mechanical allodynia in mice
【24h】

Spinal astrocytic activation contributes to both induction and maintenance of pituitary adenylate cyclase-activating polypeptide type 1 receptor-induced long-lasting mechanical allodynia in mice

机译：脊髓星形胶质细胞激活有助于诱导和维持垂体腺苷酸环化酶激活多肽1型受体诱导的小鼠持久机械异常性疼痛

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are present in the spinal dorsal horn and dorsal root ganglia, suggesting an important role of PACAP–PACAP receptors signaling system in the modulation of spinal nociceptive transmission. We have previously reported that a single intrathecal injection of PACAP or a PACAP specific (PAC1) receptor selective agonist, maxadilan, in mice induced dose-dependent aversive behaviors, which lasted more than 30?min, and suggested that the maintenance of the nociceptive behaviors was associated with the spinal astrocytic activation. We found that a single intrathecal administration of PACAP or maxadilan also produced long-lasting hind paw mechanical allodynia, which persisted at least 84 days without affecting thermal nociceptive threshold. In contrast, intrathecal application of vasoactive intestinal polypeptide did not change mechanical threshold, and substance P, calcitonin gene-related peptide, or N-methyl-D-aspartate induced only transient mechanical allodynia, which disappeared within 21 days. Western blot and immunohistochemical analyses with an astrocytic marker, glial fibrillary acidic protein, revealed that the spinal PAC1 receptor stimulation caused sustained astrocytic activation, which also lasted more than 84 days. Intrathecal co-administration of L-α-aminoadipate, an astroglial toxin, with PACAP or maxadilan almost completely prevented the induction of the mechanical allodynia. Furthermore, intrathecal treatment of L-α-aminoadipate at 84 days after the PAC1 stimulation transiently reversed the mechanical allodynia accompanied by the reduction of glial fibrillary acidic protein expression level. Our data suggest that spinal astrocytic activation triggered by the PAC1 receptor stimulation contributes to both induction and maintenance of the long-term mechanical allodynia.
机译：垂体腺苷酸环化酶激活多肽（PACAP）及其受体存在于脊髓背角和背根神经节中，提示PACAP–PACAP受体信号传导系统在调节脊髓伤害性传递中起重要作用。我们以前曾报道过在小鼠中鞘内注射一次PACAP或PACAP特异性（PAC1）受体选择性激动剂maxadilan诱导了剂量依赖性厌恶行为，持续超过30分钟，并提示维持伤害性行为与脊髓星形细胞活化有关。我们发现，单次鞘内注射PACAP或maxadilan也会产生持久的后爪机械性异常性疼痛，该异常持续至少84天而不会影响热伤害阈值。相反，鞘内施用血管活性肠多肽不会改变机械阈值，P物质，降钙素基因相关肽或N-甲基-D-天门冬氨酸仅诱导短暂的机械性异常性疼痛，在21天内消失。使用星形胶质纤维酸性蛋白的星形胶质细胞蛋白质印迹和免疫组织化学分析显示，脊髓PAC1受体刺激引起持续的星形胶质细胞活化，持续时间也超过84天。鞘内共同施用L-α-氨基己二酸（一种星形胶质毒素）与PACAP或maxadilan几乎完全阻止了机械性异常性疼痛的诱导。此外，在PAC1刺激后第84天进行鞘内治疗L-α-氨基己二酸酯可暂时逆转机械性异常性疼痛，并伴有胶质纤维酸性蛋白表达水平降低。我们的数据表明由PAC1受体刺激触发的脊髓星形细胞活化既有助于诱导和维持长期的机械性异常性疼痛。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号