Danziger Nicolas, Gautron Michèle, Le Bars Daniel, Bouhassira Didier
INSERM U-161, 2 rue d'Alésia, 75014 Paris, France.
Pain. 2001 Apr;91(3):287-296. doi: 10.1016/S0304-3959(00)00451-6.
Diffuse noxious inhibitory controls (DNIC), which involve supraspinal structures and modulate the transmission of nociceptive signals, were investigated in rats with chronic constriction injury of the sciatic nerve. Nerve-injured rats with increased sensitivity to mechanical and thermal stimulation on the operated side were anesthetized and recordings were made from trigeminal convergent neurons. Inhibitions of C-fiber-evoked neuronal responses during and after the application of nociceptive conditioning stimuli to the hindpaw, were measured to evaluate DNIC. The conditioning stimuli consisted of graded natural (pressure and heat) and electrical stimuli and were applied alternately to non-operated and operated hindpaws. Compared with the non-operated paw, inhibitions elicited by pressure on the operated hindpaw were increased significantly at all stimulus intensities. Albeit to a lesser extent, inhibitions elicited by thermal stimulation of the operated paw were also increased in the nerve-injured animals. Such exacerbation of DNIC-induced inhibitions produced by mechanical and thermal stimulation of the operated paw can be explained by an increase in the afferent input to the spinal cord. In contrast to the results obtained with natural stimulations, inhibitions evoked from the operated and non-operated paws were similar when graded electrical stimulation was used as the conditioning stimulus. This was true regardless of the intensity and frequency of stimulation and regardless of whether the stimuli were applied transcutaneously or directly to the sciatic nerve. The clear-cut difference between the results obtained with natural and electrical conditioning stimuli suggests that the nociceptive neurons involved in the triggering of DNIC may not be sensitized at the central level. Peripheral mechanisms such as the sensitization of nerve injured fibers and/or sprouting of nerve terminals may thus be the main causes of DNIC increase in this model of neuropathic pain.
在坐骨神经慢性压迫损伤的大鼠中，对涉及脊髓上结构并调节伤害性信号传递的弥漫性有害抑制控制（DNIC）进行了研究。对手术侧机械和热刺激敏感性增加的神经损伤大鼠进行麻醉，并从三叉会聚神经元进行记录。通过测量后爪施加伤害性条件刺激期间和之后C纤维诱发的神经元反应的抑制作用，来评估DNIC。条件刺激包括分级的自然刺激（压力和热）和电刺激，并交替施加于未手术和手术的后爪。与未手术的爪子相比，在所有刺激强度下，手术侧后爪施加压力引起的抑制作用均显著增加。尽管程度较轻，但在神经损伤的动物中，手术侧爪子热刺激引起的抑制作用也有所增加。手术侧爪子机械和热刺激引起的DNIC诱导抑制作用的这种加剧，可以通过脊髓传入输入的增加来解释。与自然刺激获得的结果相反，当使用分级电刺激作为条件刺激时，手术侧和未手术侧爪子诱发的抑制作用相似。无论刺激的强度和频率如何，也无论刺激是经皮施加还是直接施加于坐骨神经，都是如此。自然条件刺激和电条件刺激获得的结果之间的明显差异表明，参与触发DNIC的伤害性神经元在中枢水平可能未被致敏。因此，诸如神经损伤纤维的致敏和/或神经末梢的发芽等外周机制，可能是这种神经性疼痛模型中DNIC增加的主要原因。
