Behavioral and electrophysiological assessment of hyperalgesia and changes in dorsal horn responses following partial sciatic nerve ligation in rats

Abstract

Behavioral and electrophysiological methods were used to investigate the hyperalgesia and allodynia, and functional changes in lumbar spinal dorsal horn neurons, in a model of neuropathic pain (Selzer et al. 1990) involving ligation of one-third to one-half of one sciatic nerve in rats. One and 5 weeks following ligation, there was a significant reduction in hind limb withdrawal latency to noxious radiant heat on the operated side and, to a lesser degree, on the unoperated side. By 16 weeks, heat withdrawal latencies were reduced about equally (∼ 40%) on both sides. Withdrawal threshold to mechanical pressure was markedly reduced within 1 week on the operated side, and decreased in a time-dependent manner on the unoperated side. Heat withdrawal latency and von Frey withdrawal thresholds were not significantly affected in sham-operated rats. The same rats were tested in a paradigm measuring the isometric force of hind limb withdrawals elicited by graded noxious contact heat stimuli (38–52°C, 5 sec). Withdrawal force increased monotonically with stimulus temperature starting at a threshold of ∼ 40°C. Stimulus-response functions were not significantly different between a sham-operated group and groups tested 5 (acute) and 16 weeks (chronic) after partial sciatic nerve ligation. Following behavioral testing, the animals were deeply anesthetized with pentobarbital sodium to allow electrophysiological recording of responses of single lumbar dorsal horn wide-dynamic range-type neurons to mechanical and noxious thermal stimulation of the hind paw. Recordings were made from 6 sham-operated rats (26 neurons ipsilateral and 31 contralateral to the operated leg), from 7 rats receiving sciatic nerve ligation 5 weeks previously (29 ipsilateral and 29 contralateral to ligation), and from 7 rats receiving partial sciatic ligation 16 weeks previously (18 ipsilateral, 29 contralateral to ligation). In several ligated rats we were unable to find heat-responsive neurons with cutaneous receptive fields on the hind paw ipsilateral to the ligation. For the neurons that were sensitive to heat, responses increased monotonically from a threshold of 40–42°C. Neuronal stimulus-response functions for heat were not significantly different between ipsi- and contralateral (to operated) sides in the sham, 5-week or 16-week post-ligation groups, or between sham and 5- or 16-week post-ligation groups. Mechanical receptive field areas were not significantly different between ipsi- and contralateral sides in the sham and 5-week post-ligation groups, or between sham and 5-week post-ligation groups. However, receptive field areas were significantly larger in the 16-week post-ligation group (both ipsi- and contralateral to ligation) compared to sham and 5-week post-ligation groups. The results suggest that allodynia may be associated with a chronic enhancement of neuronal mechanosensitivity, but that the thermal hyperalgesia is not associated with enhanced neuronal responsiveness or force of withdrawal.