NOXIOUS THERMAL AND CHEMICAL-STIMULATION INDUCE INCREASES IN H-3 PHORBOL 12,13-DIBUTYRATE BINDING IN SPINAL-CORD DORSAL HORN AS WELL AS PERSISTENT PAIN AND HYPERALGESIA, WHICH IS REDUCED BY INHIBITION OF PROTEIN-KINASE-C

We have previously suggested that protein kinase C (PKC) contributes t o persistent pain in the formalin test. This study compared the effect s of pharmacological inhibition of PKC with either GF 109203X or chele rythrine on persistent pain following noxious chemical stimulation wit h its effects on mechanical hyperalgesia, which develops in the hindpa w contralateral to an injury produced by noxious thermal stimulation, Furthermore, we have assessed changes in membrane-associated PKC in sp inal cord in response to both noxious chemical and thermal stimulation . Nociceptive responses, to a hindpaw injection of 50 mu l of 2.5% for malin, and flexion reflex thresholds, to mechanical stimulation (Randa ll-Selitto test) in the hindpaw contralateral to a thermal injury (15 sec immersion in water at 55 degrees C), were assessed following intra thecal injection of PKC inhibitors (GF 109203X or chelerythrine). Chan ges in the levels of membrane-associated PKC, as assayed by quantitati ve autoradiography of the specific binding of H-3-phorbol-12,13-dibuty rate (H-3-PDBu) in spinal cord sections, were assessed in rats after n oxious chemical (50 mu l of 5.0% formalin) and noxious thermal (90 sec immersion in water at 55 degrees C) stimulation, Inhibitors of PKC (G F 109203X, chelerythrine), produced significant reductions of nocicept ive responses to 2.5% formalin, as well as a significant reduction in the mechanical hyperalgesia in the hindpaw contralateral to a thermal injury, In addition, both noxious chemical and thermal stimulation pro duced significant increases in specific H-3-PDBu binding in the dorsal horn of the lumbar spinal cord, likely reflecting alterations in memb rane-associated PKC, The results provide both pharmacological and anat omical evidence that persistent pain produced by chemical stimulation with formalin and mechanical hyperalgesia in the hindpaw contralateral to a thermal injury are influenced by the translocation and activatio n of PKC in spinal cord dorsal horn neurons.