Remarkably long-lasting tachyphylaxis of pain responses to ET-1: evidence against central nervous system involvement.
Remarkably long-lasting tachyphylaxis of pain responses to ET-1: evidence against central nervous system involvement.
复制标题
对 ET-1 疼痛反应的显着持久的快速耐受：反对中枢神经系统参与的证据。
DOI：
10.1139/y10-044
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发表时间：
2010
影响因子：
2.1
通讯作者：
Strichartz,GaryR
中科院分区：
文献类型：
--
作者：
Khodorova,Alla;Strichartz,GaryR
足底皮下注射内皮素-1(ET-1)引起的急性良性退缩(疼痛)反应，在第二次注射时反应减弱，这是一种深刻的快速反应。在24、30、48和72h4个时间点，第二次注射的缩短率分别为第一次注射的20%±5%、57%±18%、79%±35%和100%±17%。局部麻醉坐骨神经局部麻醉抑制传入冲动，使最初的缩腿反应减少到对照组的6%~13%，但不影响第二次注射后24小时的快速反应。第二次注射ET-1前30min给予纳洛酮(5-8 mg/kg，ip)抑制内源性阿片类药物的下行抑制作用，但不能阻止快速反应。尾部或前爪皮下注射ET-1引起的弥散效应导致后爪对ET-1的反应敏化，而不是快速反应。相反，用拮抗剂BQ-123(3.2 mmol/L)选择性地抑制ET-1初始给药过程中的局部ETA受体，可减少痛觉退缩的快速反应。因此，长时间的疼痛快速反应并不是由于中枢神经系统的反应性降低，而是取决于外周ETA受体的功能敏感性或可用性。
A profound tachyphylaxis of the acute nocifensive flinching (pain) response to subcutaneous injection of endothelin-1 (ET-1) into the hind paw footpad is shown by the reduced response to a second injection. Flinching from the second injection was 20% ± 5%, 57% ± 18%, 79% ± 35%, and 100% ± 17% of that from the first injection (both 200 µmol/L, 2 nmol) at respective intervals of 24, 30, 48, and 72 h. Inhibition of afferent impulses by local anesthesia of the sciatic nerve, reducing initial flinching to 6%–13% of control, did not affect the tachyphylaxis for the second injection at 24 h. There was no cross-desensitization between formalin and ET-1 injected sequentially into the same paw. Suppression of descending inhibitory effects from endogenous opiates by naloxone (5–8 mg/kg, i.p.), given 30 min before the second ET-1 injection, did not prevent tachyphylaxis. Diffuse effects caused by an initial subcutaneous ET-1 injection into the tail or forepaw resulted in sensitization of the response to ET-1 in the hind paw, rather than tachyphylaxis. In contrast, selective inhibition of local ETAreceptors during the initial administration of ET-1, by the antagonist BQ-123 (3.2 mmol/L), reduced tachyphylaxis of nocifensive flinching. Therefore, prolonged pain tachyphylaxis is not due to reduced responsiveness of the CNS, but rather depends on the functional sensitivity or availability of peripheral ETAreceptors.