Miao F J, Jänig W, Jasmin L, Levine J D
Department of Medicine, NIH Pain Center, University of California at San Francisco, CA 94143-0440, USA.
J Physiol. 2001 May 1;532(Pt 3):811-22. doi: 10.1111/j.1469-7793.2001.0811e.x.
Stimulation of nociceptors by intradermal capsaicin produces depression of bradykinin (BK)-induced synovial plasma extravasation (PE) that is markedly enhanced by subdiaphragmatic vagotomy. This depression is mediated by the adrenal medullae, a propriospinal pathway between the afferent nociceptive input and preganglionic neurones projecting to the adrenal medullae, and a spino-bulbo-spinal pathway. Here we investigated the role of spinal ascending and descending pathways in the interaction between noxious and vagal afferent inputs, leading to inhibition of BK-induced PE mediated by the adrenal medullae. Nociceptors in the paw were activated by capsaicin and depression of BK-induced PE was measured in rats with intact or cut subdiaphragmatic vagus nerves. After cutting the dorsolateral funiculus (DLF) contralateral to the stimulated hindpaw (segmental level C5/C6 and T8/T9), depression of BK-induced PE was weak or absent both in rats with intact vagus nerves and in vagotomised rats, suggesting that an ascending excitatory pathway was interrupted. After cutting the DLF ipsilateral to the stimulated hindpaw, depression of BK-induced PE was already markedly enhanced, even in the absence of vagotomy. Ipsilateral DLF lesion (L2/L3) below the level of the spinal output to the adrenal medullae produced the same effect, suggesting interruption of a descending inhibitory pathway that relays the effect of vagal activity to the level of the capsaicin-induced nociceptive input. Contralateral and ipsilateral hemisection of the spinal cord (C5/C6) produced the same changes as the corresponding DLF lesions. Ipsi- or contralateral lesion of the dorsal funiculus at the spinal level T8/T9 had no effect on depression of BK-induced PE generated by cutaneous noxious stimulation of the forepaw. We suggest that noxious stimulation activates an ascending pathway of the spino-bulbo-spinal excitatory circuit which projects through the DLF contralateral to the nociceptive input, and that the inhibitory pathway which is activated by vagal afferent activity projects through the DLF ipsilateral to the nociceptive input.
皮内注射辣椒素刺激伤害感受器可抑制缓激肽（BK）诱导的滑膜血浆外渗（PE），而膈下迷走神经切断术可显著增强这种抑制作用。这种抑制作用由肾上腺髓质、传入伤害性输入与投射至肾上腺髓质的节前神经元之间的脊髓固有通路以及脊髓-延髓-脊髓通路介导。在此，我们研究了脊髓上行和下行通路在伤害性和迷走传入输入相互作用中的作用，这种相互作用导致肾上腺髓质介导的BK诱导的PE受到抑制。通过辣椒素激活爪部的伤害感受器，并在膈下迷走神经完整或切断的大鼠中测量BK诱导的PE的抑制情况。在切断与受刺激后爪对侧的背外侧索（DLF）（节段水平C5/C6和T8/T9）后，无论是迷走神经完整的大鼠还是迷走神经切断的大鼠，BK诱导的PE的抑制作用均减弱或消失，这表明一条上行兴奋性通路被中断。在切断与受刺激后爪同侧的DLF后，即使在未进行迷走神经切断术的情况下，BK诱导的PE的抑制作用也已显著增强。在脊髓向肾上腺髓质输出水平以下的同侧DLF损伤（L2/L3）产生了相同的效果，这表明一条下行抑制通路被中断，该通路将迷走神经活动的效应传递至辣椒素诱导的伤害性输入水平。脊髓（C5/C6）的对侧和同侧半横断产生了与相应DLF损伤相同的变化。在脊髓水平T8/T9处同侧或对侧的背索损伤对前爪皮肤伤害性刺激产生的BK诱导的PE的抑制作用没有影响。我们认为，伤害性刺激激活了脊髓-延髓-脊髓兴奋性回路的一条上行通路，该通路通过与伤害性输入对侧的DLF投射，而由迷走传入活动激活的抑制性通路则通过与伤害性输入同侧的DLF投射。
