Pertovaara A
Department of Physiology, University of Helsinki, Finland.
Exp Neurol. 1998 Jan;149(1):193-202. doi: 10.1006/exnr.1997.6688.
Tissue injury produces hyperalgesia not only in the injured area (primary hyperalgesia) but also outside of it (secondary hyperalgesia). In the present investigation, the submodality selectivity and the contribution of supraspinal influence to a neural correlate of the secondary hyperalgesia induced by neurogenic inflammation was studied in the presumed pain relay neurons of the rat spinal dorsal horn. Mechanically and thermally evoked responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were recorded under sodium pentobarbital anesthesia in rats. Neurogenic inflammation was induced by application of mustard oil outside of the receptive fields of WDR neurons. To study the contribution of supraspinal influence to mustard oil-induced changes in neuronal responses, the spinal cord was transected at a midthoracic level or lidocaine was microinjected into the rostroventromedial medulla (RVM). Furthermore, the antidromically evoked compound volley in the sural nerve was determined to reveal excitability changes in the central terminals of primary afferent A-fibers induced by mustard oil. The results indicate that mustard oil adjacent to the receptive fields of spinal WDR neurons significantly enhanced their responses to mechanical but not to noxious heat stimuli, without a significant influence on their spontaneous activity. Both high- and low-threshold mechanoreceptive input to WDR neurons was equally facilitated, whereas mechanoreceptive input to spinal dorsal horn neurons mediating innocuous messages (low-threshold mechanoreceptive neurons) was not changed. Mustard oil in a remote site (forepaw) did not produce any hyperexcitability to responses evoked by hindpaw stimulation. Spinal transection or lidocaine block of the RVM significantly attenuated the mustard oil-induced mechanical hyperexcitability in spinal dorsal horn neurons. Mustard oil had no significant effect on a compound volley in the sural nerve induced by intraspinal stimulation of sural nerve terminals at a submaximal intensity. The selective mechanical hyperexcitability in spinal WDR neurons, without a change in their spontaneous activity, can be explained by a heterosynaptic facilitatory action on presynaptic terminals mediating mechanical signals to these nociceptive spinal neurons. These findings indicate that brain stem-spinal pathways, involving the RVM, do not only suppress nociception but under some pathophysiological conditions concurrent facilitatory influence may predominate and lead to enhancement of mechanical hyperexcitability. The descending facilitatory feed-back loop to nociceptive spinal neurons may help to protect the wounded tissue and thus promote healing.
组织损伤不仅会在损伤区域产生痛觉过敏（原发性痛觉过敏），还会在损伤区域之外产生（继发性痛觉过敏）。在本研究中，我们在大鼠脊髓背角假定的痛觉传导神经元中，研究了神经源性炎症诱导的继发性痛觉过敏的亚模式选择性以及脊髓上影响对其神经关联物的作用。在戊巴比妥钠麻醉下，记录大鼠脊髓背角广动力范围（WDR）神经元对机械和热刺激的诱发反应。通过在WDR神经元感受野之外涂抹芥子油来诱导神经源性炎症。为了研究脊髓上影响对芥子油诱导的神经元反应变化的作用，在胸段中部水平横断脊髓，或将利多卡因微量注射到延髓头端腹内侧（RVM）。此外，测定腓肠神经的逆向诱发复合波，以揭示芥子油诱导的初级传入A纤维中枢终末兴奋性变化。结果表明，与脊髓WDR神经元感受野相邻的芥子油显著增强了它们对机械刺激而非有害热刺激的反应，对其自发活动没有显著影响。WDR神经元的高阈值和低阈值机械感受性输入均得到同等程度的促进，而介导无害信息的脊髓背角神经元（低阈值机械感受性神经元）的机械感受性输入未发生变化。在远处部位（前爪）涂抹芥子油，对后爪刺激诱发的反应未产生任何兴奋性增强。脊髓横断或RVM的利多卡因阻断显著减弱了芥子油诱导的脊髓背角神经元的机械性兴奋性增强。芥子油对以次最大强度脊髓内刺激腓肠神经终末诱发的腓肠神经复合波没有显著影响。脊髓WDR神经元中选择性的机械性兴奋性增强，而其自发活动未改变，这可以通过对介导机械信号至这些伤害性脊髓神经元的突触前终末的异突触易化作用来解释。这些发现表明，涉及RVM的脑干 - 脊髓通路不仅抑制痛觉，而且在某些病理生理条件下，同时存在的易化性影响可能占主导，并导致机械性兴奋性增强。对伤害性脊髓神经元的下行易化反馈回路可能有助于保护受伤组织，从而促进愈合。
