Sensory and sympathetic contributions to nerve injury-induced sensory abnormalities in the rat.

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.