Picrotoxin produces a "central" pain-like syndrome when microinjected into the somato-motor cortex of the rat.

In this study, we report the possibility of producing marked electrocorticographic changes and "pain-like" reactions, when the GABAA antagonist picrotoxin is microinjected unilateraly into the rat somato-motor Sml cortex in the region of the hind paw. After the microinjection, we observed continuous seizure isolated spikes, spikes-and-waves, bursts, and pain-like reactions, almost exclusively confined to the hind paw. These reactions considered of lifting off the floor, licking of the paw palm or digits, biting, paw tremors, and a peculiar paw position that we called "turn-in" paw. We also noted other behaviors, such as "limping," "neglected" paw, or rearing. The "pain-like" character of these manifestations was suggested by the fact that similar qualitative and quantitative data occurred consequent to the administration of 2.5% diluted formalin into the palm of the hind paw in different rats. Bringing together the electrocorticographic events and the behavioral reactions produced by Sml picrotoxin indicated that there was no obvious correlation between the phenomena, except that the tremor was always associated with the bursts. Sensory denervation of the hind paw, produced by sciatic and saphenous nerve transections, did not significantly modify either the ictal activity or the behavior. Finally, microinjection of naloxone prior to picrotoxin did not change the cortical events, but greatly diminished the "pain-like" reactions. All these results favor the cortical microinjection of a GABAA receptor antagonist as a good rat model for studying pain of "central" origin. They emphasize the possible role of the Sml cortex in such a phenomenon, and the deficit of cortical GABAergic processing, which can include an opioid link.