Kinnman E, Levine J D
Department of Anatomy, University of California, San Francisco 94143, USA.
Neuroscience. 1995 Feb;64(3):751-67. doi: 10.1016/0306-4522(94)00435-8.
Peripheral neuropathy can be associated with a variety of symptoms, including spontaneous unpleasant sensations and pain, as well as increased sensitivity to sensory stimuli. A peripheral neuropathy model involving an L5 spinal nerve lesion in male rats has been used to gain insight into the mechanisms that underlie symptoms that develop after nerve injury. This model was used to study the involvement of sensory fibres, the sympathetic postganglionic neuron and the role of nerve growth factor in the induction and maintenance of altered sensory function in the nerve territory of the intact L4 spinal nerve. Sensory testing was done with calibrated von Frey filaments and a radiant heat apparatus [Hargreaves K. et al. (1988) Pain 32, 77-88] and the occurrence of abnormal spontaneous behaviour was recorded. L5 spinal nerve resection produced increased mechanical and heat sensitivity as well as abnormal spontaneous behaviours. Surgical sympathectomy at the L5 but not at the L4 spinal nerve level alleviated all sensory abnormalities. However, a lesion of preganglionic fibres to the L5 level had no significant effect on sensory abnormalities. Thus, sympathetic postganglionic neurons at the level of spinal nerve injury can contribute to neuropathy symptoms independent of input from preganglionic neurons. Postganglionic sympathetic nerve crush alone led to increased mechanical sensitivity but not to increased heat sensitivity nor to abnormal spontaneous behaviour, further emphasizing the role of sympathetic postganglionic neuron changes for the development of increased mechanical sensitivity. An L5 spinal nerve resection in rats treated neonatally with capsaicin induced increased mechanical sensitivity which was slower in onset and lower in magnitude than that in untreated littermates and was abolished by postganglionic sympathectomy. Nerve growth factor perfused onto the cut L5 spinal nerve also markedly delayed the onset of increased mechanical sensitivity. Two pathophysiological mechanisms leading to central changes may be necessary to produce altered sensations in this model: (i) ongoing activity in C-fibres, independent of sympathetic postganglionic neuron activity and (ii) activity in sensory fibres modulated by a sensory-sympathetic interaction in the injured spinal nerve or dorsal root ganglion. The sympathetic postganglionic neuron contribution is independent of preganglionic sympathetic outflow from the central nervous system, suggesting a novel mechanism by which sympathetic efferent terminals can regulate sensory fibre activity. A contribution of a loss of neurotrophic factors to the sympathetic postganglionic neuron following nerve lesion is also suggested to contribute to the symptoms induced by the spinal nerve lesion.
周围神经病变可能与多种症状相关，包括自发的不适感和疼痛，以及对感觉刺激的敏感性增加。一种涉及雄性大鼠L5脊神经损伤的周围神经病变模型已被用于深入了解神经损伤后出现的症状背后的机制。该模型用于研究感觉纤维、交感神经节后神经元的参与情况，以及神经生长因子在完整L4脊神经支配区域感觉功能改变的诱导和维持中的作用。使用校准的von Frey细丝和辐射热装置[哈格里夫斯K.等人（1988年），《疼痛》32卷，77 - 88页]进行感觉测试，并记录异常自发行为的发生情况。L5脊神经切断术导致机械敏感性和热敏感性增加以及异常自发行为。在L5而非L4脊神经水平进行手术交感神经切除术可缓解所有感觉异常。然而，L5水平的节前纤维损伤对感觉异常无显著影响。因此，脊神经损伤水平的交感神经节后神经元可独立于节前神经元的输入而导致神经病变症状。单独的节后交感神经挤压导致机械敏感性增加，但热敏感性未增加，也未出现异常自发行为，进一步强调了交感神经节后神经元变化在机械敏感性增加发展中的作用。用辣椒素对新生大鼠进行处理后进行L5脊神经切断术，会导致机械敏感性增加，但其起效较慢且程度低于未处理的同窝大鼠，并且节后交感神经切除术可消除这种增加。将神经生长因子灌注到切断的L5脊神经上也显著延迟了机械敏感性增加的起效时间。在该模型中，可能需要两种导致中枢变化的病理生理机制来产生感觉改变：（i）C纤维的持续活动，独立于交感神经节后神经元活动；（ii）在受损脊神经或背根神经节中由感觉 - 交感相互作用调节的感觉纤维活动。交感神经节后神经元的作用独立于中枢神经系统的节前交感神经输出，这表明交感传出末梢调节感觉纤维活动的一种新机制。还提示神经损伤后神经营养因子对交感神经节后神经元的丧失也有助于脊神经损伤诱导的症状。
