Calcitonin gene-related peptide is involved in the spinal processing of mechanosensory input from the rat's knee joint and in the generation and maintenance of hyperexcitability of dorsal horn neurons during development of acute inflammation
Calcitonin gene-related peptide is involved in the spinal processing of mechanosensory input from the rat's knee joint and in the generation and maintenance of hyperexcitability of dorsal horn neurons during development of acute inflammation
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DOI：
10.1016/0306-4522(95)00473-4
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发表时间：
1996-04-01
期刊：
影响因子：
3.3
通讯作者：
Schaible, HG
中科院分区：
文献类型：
--
作者：
Neugebauer, V;Rumenapp, P;Schaible, HG
在麻醉大鼠的电生理研究中，研究了降钙素基因相关肽参与正常和炎症膝关节的机械感觉信息的脊髓处理。降钙素基因相关肽（8-37）是降钙素基因相关肽I受体的特异性拮抗剂，在膝关节内注射高岭土和角叉菜胶诱导的膝关节急性炎症发生之前、期间和之后，将降钙素基因相关肽（8- 37）以离子电泳的方式施用到接近于具有来自膝关节的输入的伤害感受神经元。降钙素基因相关肽（8-37）选择性拮抗离子导入降钙素基因相关肽的作用，但不拮抗离子导入P物质、神经激肽A和（R，S）-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸的作用。在炎症发生前，降钙素基因相关肽（8-37）降低了23个神经元中的22个对施加于膝关节的伤害性压力的反应; 22个神经元中的14个对无害压力的反应也降低了。在8个神经元降钙素基因相关肽（8-37）的诱导期间，并在前90分钟内的炎症的三个阶段。在这些神经元中，发展中的炎症诱发了显着较小的增加的反应，施加到注射的膝盖比在13个对照神经元，没有处理的拮抗剂在诱导炎症的无害和有害的压力。在16个神经元中，降钙素基因相关肽（8-37）在脊髓神经元的炎症和兴奋性建立后，能降低对无害和有害压力的反应，表明降钙素基因相关肽参与了正常关节机械感觉输入的脊髓加工过程。此外，该肽及其脊髓受体在炎症发展过程中显著促进炎症诱发的脊髓神经元过度兴奋的产生和表达。最后，降钙素基因相关肽参与维持炎症诱发的过度兴奋。通过这些作用，降钙素基因相关肽受体可能显着有助于与炎症相关的痛觉过敏和异常性疼痛的神经元基础。
In an electrophysiological study in anaesthetized rats, the involvement of calcitonin gene-related peptide in the spinal processing of mechanosensory information from the normal and inflamed knee joint was investigated. Calcitonin gene-related peptide(8-37), a specific antagonist at calcitonin gene-related peptide I receptors was administered ionophoretically close to nociceptive neurons with input from the knee joint before, during, and after development of acute inflammation in the knee induced by the intra-articular injections of kaolin and carrageenan. Calcitonin gene-related peptide(8-37) selectively antagonized the effects of ionophoretically applied calcitonin gene-related peptide but not those of ionophoretically applied substance P, neurokinin A, and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid. Before inflammation, calcitonin gene-related peptide(8-37) reduced the responses to noxious pressure applied to the knee in 22 of 23 neurons; in 14 of 22 neurons, the responses to innocuous pressure were also reduced. In eight neurons calcitonin gene-related peptide(8-37) was administered during induction and in three periods within the first 90 min of inflammation. In these neurons the developing inflammation evoked a significantly smaller increase of the responses to innocuous and noxious pressure applied to the injected knee than in 13 control neurons which were not treated by the antagonist during induction of inflammation. In 16 of 16 neurons, calcitonin gene-related peptide(8-37) reduced the responses to innocuous and noxious pressure once inflammation and hyperexcitability of the spinal cord neurons were established.These data show that calcitonin gene-related peptide is involved in the spinal processing of mechanosensory input from the normal joint. Furthermore, this peptide and its spinal receptors significantly contribute to the generation and expression of inflammation-evoked hyperexcitability of spinal cord neurons during the development of inflammation. Finally, calcitonin gene-related peptide is involved in the maintenance of inflammation-evoked hyperexcitability. By these effects calcitonin gene-related peptide receptors may significantly contribute to the neuronal basis of hyperalgesia and allodynia associated with inflammation.