Unilateral dorsal rhizotomy of brachial plexus nerves (C5-Th1) performed under general anesthesia is known to induce self-mutilation in rats. The aim of this study was to determine the effect of different anesthetic agents, and of pre-rhizotomy nociceptive stimulation on the appearance of self-mutilation. Self-mutialtion appeared in 78 % of animals after rhizotomy had been performed under pentobarbital anesthesia. When ketamine was used as the general anesthetic, self-mutilation was almost suppressed (13 %) and consisted of superficial erosions. Mechanical nociceptive stimulation, when applied just before the induction of ketamine anesthesia and subsequent rhizotomy, provoked self-mutilation in 91 % of rats. Furthermore, a serious type of self-mutilation consisting of total amputation of the distal part of the forepaw was present in 28 % of all self-mutilating animals after previous nociceptive stimulation. In terms of self-mutilation, these results suggest 1) the crucial role of anesthesia, especially that which involved NMDA receptors (ketamine), and 2) the need of an additional factor to chronic deafferentation, formed either by activity of nociceptive pathways just before rhizotomy (nociceptive stimulation preceding ketamine anesthesia) or by injury discharges (pentobarbital anesthesia).
Baclofen, which is a specific agonist of the metabotropic GABAB receptor, is used in clinical practice for the treatment of spasticity of skeletal muscles. It also exerts an analgesic effect, but this effect is still not clear and especially controversial in neuropathic pain. In this work, we studied the antinociceptive effects of baclofen in a model of chronic peripheral neuropathic pain – loose ligation of the sciatic nerve (chronic constriction injury, CCI). As controls we used sham-operated animals. The changes of thermal pain threshold were measured using the plantar test 15-25 days after the operation. The obtained results suggest that baclofen increases pain threshold in both groups. The antinociceptive effect of baclofen was dose-dependent and the maximum response without motor deficits was observed at a dose of 15 mg/kg s.c. In the rats with CCI, significant differences between affected (ipsilateral) and contralateral hind paw were present. This difference was dose-dependent, the highest value (6.2±1.37 s) was found at the dose of 20 mg/kg. Based on our results and previous findings it could be summarized that baclofen has antinociceptive action, which is attenuated in the model of chronic neuropathic pain probably due to the degeneration of GABA interneurons after chronic constriction injury.