Tumor-evoked Sensitization of C nociceptors: A role for endothelin
Tumor-evoked Sensitization of C nociceptors: A role for endothelin
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DOI：
10.1152/jn.01337.2007
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发表时间：
2008-10-01
影响因子：
2.5
通讯作者：
Simone, Donald A.
中科院分区：
文献类型：
--
作者：
Hamamoto, Darryl T.;Khasabov, Sergey G.;Simone, Donald A.
影响骨骼的原发癌和转移癌常常与疼痛有关。支配肿瘤附近组织的初级传入C伤害性感受器的敏化可能导致伴随这种情况的慢性疼痛和痛觉过敏。本研究旨在探讨内源性多肽内皮素-1(ET-1)作为一种潜在的外周变应原在癌痛过程中的作用。在麻醉对照组小鼠和将纤维肉瘤细胞植入跟骨及其周围后表现出机械性痛觉过敏的小鼠的胫神经上，记录了C伤害性感受器的电生理反应特性，包括持续活动和热刺激引起的反应。将ET-1(100µM)注射到支配后爪足底表面的C伤害性感受器的感受野中，可引起对照组和荷瘤小鼠持续活动的增加。此外，选择性ET A受体拮抗剂BQ-123(3 MM)可减弱荷瘤小鼠肿瘤诱发的持续活动。ET-1使对照组小鼠的C伤害性感受器对热刺激增敏，而荷瘤小鼠的C伤害性感受器对热敏感，ET-1不能进一步增强其反应。重要的是，给予BQ-123可减弱肿瘤引起的C伤害性感受器对热的敏感化。我们的结论是，肿瘤部位的ET-1通过ET A受体介导的机制参与了肿瘤诱发的C伤害性感受器的兴奋和增敏。
Primary and metastatic cancers that effect bone are frequently associated with pain. Sensitization of primary afferent C nociceptors innervating tissue near the tumor likely contributes to the chronic pain and hyperalgesia accompanying this condition. This study focused on the role of the endogenous peptide endothelin-1 (ET-1) as a potential peripheral algogen implicated in the process of cancer pain. Electrophysiological response properties, including ongoing activity and responses evoked by heat stimuli, of C nociceptors were recorded in vivo from the tibial nerve in anesthetized control mice and mice exhibiting mechanical hyperalgesia following implantation of fibrosarcoma cells into and around the calcaneus bone. ET-1 (100 mu M) injected into the receptive fields of C nociceptors innervating the plantar surface of the hind paw evoked an increase in ongoing activity in both control and tumor-bearing mice. Moreover, the selective ET A receptor antagonist, BQ-123 (3 mM), attenuated tumor-evoked ongoing activity in tumor-bearing mice. Whereas ET-1 produced sensitization of C nociceptors to heat stimuli in control mice, C nociceptors in tumor-bearing mice were sensitized to heat, and their responses were not further increased by ET-1. Importantly, administration of BQ-123 attenuated tumor-evoked sensitization of C nociceptors to heat. We conclude that ET-1 at the tumor site contributes to tumor-evoked excitation and sensitization of C nociceptors through an ET A receptor mediated mechanism.