NORMAL AND PRECOCIOUS SPROUTING OF HEAT NOCICEPTORS IN THE SKIN OF ADULT-RATS

NORMAL AND PRECOCIOUS SPROUTING OF HEAT NOCICEPTORS IN THE SKIN OF ADULT-RATS
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DOI:
10.1002/cne.902610410
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发表时间:
1987-07-22
影响因子:
2.5
通讯作者:
DIAMOND, J
DIAMOND, J
中科院分区:
医学3区
文献类型:
--
作者:
DOUCETTE, R;DIAMOND, J

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在成年大鼠中,研究了完整的皮肤热感C纤维向邻近无神经支配的皮肤中发芽的能力,以及轴突电活动对其的影响。背部皮肤热敏末梢的存在通过热探针引起皮下干肌反射性收缩的能力进行生理评估;感觉C纤维是通过Evens Blue技术检测到的,在这种技术中,C纤维的反激作用会导致它所提供的皮肤中染料的明显外渗,并通过直接电子显微镜(EM)检查皮肤。选择背皮神经(DCN)的一个确定分支的领域通过消除周围皮肤的所有神经被“隔离”。热敏感区在隔离后10至14天开始扩大,并在约24天达到最大值(约为初始值的两倍)。当离体神经反节律兴奋时,发生染料外渗的边界已扩大;变色面积与(扩大的)热场面积相关良好,表明其扩大确实是由于C纤维发芽。电镜检查显示,在去神经支配后不敏感皮肤的皮下水平纤维系统中,常规观察到一些“空”雪旺管,当热敏性恢复时,已获得无髓鞘轴突。如果在相邻断神经时随机对整个热场施加热刺激,则热场在分离后10天就会出现明显的早熟扩张;这种扩张也被证明是由于C纤维的发芽。如果在电场隔离之后,未受影响的DCN中的C纤维立即受到电刺激,以及如果通过其电场施加挤压,也就是说,涉及的C纤维似乎是多模态的,对热和有害的机械刺激都有反应,也会发生热致痛觉纤维的早熟萌芽。在分离的DCN中,当使用河豚毒素阻断“调节”脉冲的中央传导时,不会发生早熟发芽。周围神经损伤常发生在容易引起伤害神经激活的情况下;我们认为,除了加速提供伤害性神经支配外,备用轴突的加速发芽在减少萎缩变化可能发生在失神经靶区期间可能是重要的。各种实验方法,现在可用于生产差异神经支配的选定区域的背部皮肤进行了总结。
The ability of intact cutaneous thermonociceptive C fibers to sprout into adjacent denervated skin, and the effects on this of electrical activity in the axons, were studied in adult rats. The presence of heat-sensitive endings in the back skin was assessed physiologically by the ability of a hot probe to elicit the reflex contraction of the underlying cutaneous trunci muscle; sensory C fibers were detected both by the Evens Blue technique, in which antidromic excitation of the C fibers causes a visible extravasation of dye in the skin it supplied, and by direct electron microscope (EM) examination of skin. The field of an identified branch of a selected dorsal cutaneous nerve (DCN) was "isolated" by eliminating all the nerves supplying the surrounding skin. The heat-sensitive area began to expand between 10 and 14 days after its isolation and reached a maximum (approximately doubling the initial value) by about 24 days. When the isolated nerve was antidromically excited, the borders within which dye extravasation now occurred had extended; the area of discoloration correlated well with that of the (enlarged) heat field, showing that its expansion was indeed attributable to C fiber sprouting. Electron microscopic examination showed that some of the "empty" Schwann tubes, routinely observed in the subepidermal horizontal fiber system of insensitive skin following denervation, had acquired unmyelinated axons when heat sensitivity had returned. A precocious expansion of the heat field, which was obvious by 10 days after its isolation, was produced if the heat stimulus was applied randomly throughout the field at the time of the adjacent denervations; this expansion too was shown to be due to sprouting of C fibers. Precocious sprouting of heat-nociceptive fibers also occurred if, immediately following the field isolation, the C fibers in the spared DCN were electrically excited, and also if pinches were applied through its field, i.e., the C fibers involved seemed to be polymodal, responding both to heat and to noxious mechanical stimulation. Precocious sprouting did not occur when tetrodotoxin was used to block central conduction of the "conditioning" impulses in the isolated DCN. Peripheral nerve damage often occurs in a situation likely to cause activation of nociceptive nerves; we suggest that the accelerated sprouting of spared axons could be important in reducing the period during which atrophic changes might occur in denervated target regions, in addition to hastening the provision of a nociceptive innervation. The various experimental approaches now available for producing differential innervation of selected regions of back skin are summarized.