INVOLVEMENT OF PROTEIN-KINASE-C IN RESPONSES OF RAT DORSAL HORN NEURONS TO MECHANICAL STIMULI AND PERIAQUEDUCTAL GRAY DESCENDING INHIBITION

The effects of a protein kinase C (PKC) activator, 12-O-tetradecanoylp horbol-13-acetate (TPA), on the activity and periaqueductal gray (PAG) -induced inhibition of rat dorsal horn neurons of the lumbar spinal co rd were tested. A microdialysis fiber was placed through the dorsal ho rn for the purpose of local application of pharmacological agents. Ext racellular single-unit recordings from dorsal horn neurons were made n ear the microdialysis fiber. TPA was tested on nociceptive dorsal horn cells. There was a significant increase in the back ground activity a nd responses to ''brush'', with no changes in responses to pressure an d pinch stimuli. TPA also significantly blocked the PAG-induced inhibi tion of responses to brush, press, and pinch. These effects were elimi nated by coadministration of the PKC inhibitor NPC-15437. The solvent, which contained dimethyl sulfoxide, was also tested for its effect on the responses to peripheral mechanical stimuli and FAG-induced inhibi tion of the dorsal horn neurons. There were no significant changes. Th is experiment suggests that activation of the PKC second messenger sys tem might increase the activity of dorsal horn neurons and their respo nses to peripheral stimuli; in addition, the phorbol ester attenuated the FAG-induced descending inhibition of the dorsal horn neuron activi ty.