Peripheral mechanisms of neuropathic pain following nerve lesion: electrophysiological and behavioural experiments
In the present study the neurophysiological changes in lesioned and regenerating afferent fibres and intact afferent nerve fibres, innervating a territory adjacent to a denervated area, were investigated. Two models of nerve lesion in the rat were used: 1. The sural nerve was lesioned and the nerve fibres were allowed to regenerate to the target tissue (Regeneration Model). 2. The tibial and common peroneal nerves were ligated and sectioned, leaving the sural nerve intact (Spared Nerve Injury [SNI] Model). Spontaneous activity (SA), mechanosensitivity (MS) and thermosensitivity (TS) of the sural afferent myelinated (A-) and unmyelinated (C-) fibres were investigated neurophysiologically in vivo within both nerve lesion models. In the SNI model pain-like behaviour of the rats to mechanical and thermal stimulation of the skin was tested. A. Regeneration Model. The lesioned and regenerating MS and TS fibres with receptive fields in the lesioned nerve had lower activation thresholds and a higher incidence of SA than the intact nerve fibres in control rats. B. SNI Model. Following SNI rats developed signs of pain-like behaviour to innocuous mechanical and cold stimuli. The incidence of SA C-fibres was significantly higher, but the proportion and the activation threshold of the MS A- and C-fibres were not significantly different following SNI compared to control animals. The proportion of cold sensitive C-fibres was significantly higher and their activation threshold was significantly lower following SNI compared to control animals. These alterations might be the basis for abnormal reactions to innocuous cold stimuli of SNI rats. C. Conclusions: Neuropathic pain in patients with nerve injury may be related to increased sensitivity of lesioned and unlesioned primary afferent neurones. Unravelling the underlying cellular mechanisms of this increased sensitivity to innocuous stimuli could lead to new therapeutic tools in treatment of neuropathic pain.