Miao F J, Janig W, Levine J D
NIH Pain Centre, University of California at San Francisco, CA 94143-0440, USA.
J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):601-10. doi: 10.1111/j.1469-7793.2000.00601.x.
Recently we have found that inhibition of bradykinin-induced synovial plasma extravasation by transcutaneous electrical stimulation at strengths which excite unmyelinated afferent axons is mediated by the hypothalamo-pituitary-adrenal axis. Here we tested whether stimulation of nociceptors in the rat paw by intradermally injected capsaicin inhibits bradykinin-induced synovial plasma extravasation and whether this inhibition is mediated by the hypothalamo-pituitary-adrenal or sympatho-adrenal axis. Furthermore, we tested whether inhibition of bradykinin-induced plasma extravasation generated by intraperitoneally injected capsaicin, which preferentially excites visceral afferents, is mediated by the hypothalamo-pituitary-adrenal or sympatho-adrenal axis. We used normal rats, subdiaphragmatically vagotomized rats, rats with denervated adrenal medullae and rats with acutely transected spinal cords at the segmental levels T1/T2 or T12/L1. Injection of capsaicin into the plantar or palmar surface of the paws produced a depression of bradykinin-induced plasma extravasation. The inhibition elicited from the forepaw was larger than that from the hindpaw. The inhibition of bradykinin-induced plasma extravasation elicited from both paws was potentiated by subdiaphragmatic vagotomy. Denervation of the adrenal medullae abolished the inhibitory effect of intradermal capsaicin in vagus-intact and in vagotomized animals. After spinalization at the segmental level T1/T2, capsaicin injected into the forepaw did not depress bradykinin-induced plasma extravasation either in vagus-intact or in vagotomized animals. Capsaicin injected into the hindpaw in these spinalized animals produced a small depression. After spinalization at the segmental level T12/L1 no depression was produced by capsaicin injected into the hindpaw. Depression of bradykinin-induced plasma extravasation generated by intraperitoneal injection of capsaicin in vagus-intact and in vagotomized animals was also abolished or attenuated after denervation of the adrenal medullae. This shows that this depression was also largely dependent on the activation of the sympatho-adrenal system. We conclude that depression of bradykinin-induced plasma extravasation during stimulation of nociceptors by capsaicin is mediated predominantly by the sympathoadrenal pathway. This finding differs from the inhibitory mechanism of depression of bradykinin-induced plasma extravasation generated by cutaneous electrical stimulation, which is mediated by the hypothalamo-pituitary-adrenal axis.
最近我们发现，经皮电刺激在激发无髓传入轴突的强度下对缓激肽诱导的滑膜血浆外渗的抑制作用是由下丘脑 - 垂体 - 肾上腺轴介导的。在此，我们测试了皮内注射辣椒素对大鼠爪部伤害感受器的刺激是否会抑制缓激肽诱导的滑膜血浆外渗，以及这种抑制作用是否由下丘脑 - 垂体 - 肾上腺轴或交感 - 肾上腺轴介导。此外，我们还测试了腹腔注射辣椒素（优先激发内脏传入神经）所产生的对缓激肽诱导的血浆外渗的抑制作用是否由下丘脑 - 垂体 - 肾上腺轴或交感 - 肾上腺轴介导。我们使用了正常大鼠、膈下迷走神经切断的大鼠、肾上腺髓质去神经的大鼠以及在T1/T2或T12/L1节段水平急性横断脊髓的大鼠。将辣椒素注射到爪部的足底或掌面会导致缓激肽诱导的血浆外渗受到抑制。前爪引起的抑制作用大于后爪。膈下迷走神经切断会增强两爪对缓激肽诱导的血浆外渗的抑制作用。肾上腺髓质去神经消除了皮内辣椒素对迷走神经完整和迷走神经切断动物的抑制作用。在T1/T2节段水平脊髓横断后，注射到前爪的辣椒素在迷走神经完整或迷走神经切断的动物中均不会抑制缓激肽诱导的血浆外渗。在这些脊髓横断的动物中，注射到后爪的辣椒素会产生轻微的抑制作用。在T12/L1节段水平脊髓横断后，注射到后爪的辣椒素不会产生抑制作用。腹腔注射辣椒素在迷走神经完整和迷走神经切断的动物中所产生的对缓激肽诱导的血浆外渗的抑制作用，在肾上腺髓质去神经后也被消除或减弱。这表明这种抑制作用在很大程度上也依赖于交感 - 肾上腺系统的激活。我们得出结论，辣椒素刺激伤害感受器期间缓激肽诱导的血浆外渗的抑制作用主要由交感 - 肾上腺途径介导。这一发现不同于经皮电刺激所产生的缓激肽诱导的血浆外渗抑制作用的机制，后者是由下丘脑 - 垂体 - 肾上腺轴介导的。
