Nociceptive reaction and thermal hyperalgesia induced by local ET-1 in mice:: a behavioral and Fos study
Nociceptive reaction and thermal hyperalgesia induced by local ET-1 in mice:: a behavioral and Fos study
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DOI：
10.1007/s00210-002-0655-6
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发表时间：
2003-01-01
影响因子：
3.6
通讯作者：
Baamonde, A
中科院分区：
文献类型：
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作者：
Menéndez, L;Lastra, A;Baamonde, A
肽内皮素-1（ET 1）参与伤害性感受，而不依赖于其血管收缩作用。我们已经研究了由该肽产生的直接伤害性行为以及当在足底内（i.pl.）在小鼠中施用。这些行为测量通过定量位于注射爪子同侧的背角脊髓神经元浅层中的Fos蛋白免疫反应性来补充。ET-1诱导舔舐（60-600 pmol，i. pl.）和热痛觉过敏（20-200 pmol，i.pl.）在注射的爪中，两种作用都被ET-1与内皮素A型（ETA）受体拮抗剂BQ-123（0.3-10 nmol）的共同给药抑制，但不被内皮素B型（ET B）受体拮抗剂BQ-788（10 nmol）的共同给药抑制。此外，吗啡可剂量依赖性地抑制ET-1诱导的小鼠舔体行为。与单独应用有害热相比，对经受热刺激（55 ℃，10 s）的小鼠施用ET-1（200 pmol）增加了Fos免疫反应性脊髓背角神经元的数量。BQ-123（10 nmol）可抑制ET-1的这种作用，而BQ-788（10 nmol）则不抑制ET-1的这种作用，因此，ET-1通过ETA受体诱导伤害性行为和热痛敏。这些相同的受体似乎也参与背角神经元在热刺激下ET-1诱导的Fos免疫反应性的放大。这些结果可能有助于表征ET-1在伤害性处理中的作用，由于这种肽在疼痛状态如癌症中的病理生理参与，这是一个特别感兴趣的话题。
The peptide endothelin-1 (ET 1) has been involved in nociception independently of its vasoconstrictor effects. We have studied the direct nociceptive behavior produced by this peptide as well as its ability to induce thermal sensitisation (as measured by the unilateral hot plate method, UHP) when intraplantarly (i.pl.) administered in mice. These behavioural measures were complemented by the quantification of Fos-protein immunoreactivity in the superficial laminae of the dorsal horn spinal neurons located ipsilateral to the injected paw.ET-1 induces licking (60-600 pmol, i.pl.) and thermal hyperalgesia (20-200 pmol, i.pl.) in the injected paw, both effects being inhibited by the coadministration of ET-1 with endothelin type A (ETA) receptor antagonist, BQ-123 (0.3-10 nmol), but not with endothelin type B (ETB) receptor antagonist, BQ-788 (10 nmol). Moreover, the licking behavior induced by ET-1 was dose-dependently inhibited by the prototypical g-opioid agonist, morphine.The prior i.pl. administration of ET-1 (200 pmol) to mice subjected to thermal heat stimulus (55 1 C, 10 s) increases the number of Fos-immunoreactive dorsal horn spinal neurons compared with the application of noxious heat alone. This effect is inhibited by BQ-123 (10 nmol) but not by BQ-788 (10 nmol).Thus, local ET-1 induces nocifensive behavior and thermal hyperalgesia acting through ETA receptors. These same receptors seem to be also involved in the amplification of Fos immunoreactivity induced by ET-1 under heat stimulus in the dorsal horn neurons. These results could help to characterize the role of ET-1 in nociceptive processing, a topic of special interest due to the pathophysiological involvement of this peptide in painful states such as cancer.