The effects of phorbol ester on slowly conducting afferents of the cat's knee joint.
The effects of beta-phorbol 12,13-dibutyrate (PDBu) on the discharge properties of slowly conducting knee joint afferents (group III and group IV fibers) were studied to determine the role of protein kinase C in nociception. Extracellular single unit recordings were made from small filaments dissected from the medial articular nerve in cats anesthetized with alpha-chloralose. PDBu was applied intra-arterially close to the joint in concentrations of 10(-6) up to 10(-4) M. The afferents were classified as low-threshold and high-threshold units with regard to their sensitivity to passive noxious and innocuous movements of the knee joint. Following PDBu application, an excitation occurred in 28% of the group III and in 40% of the group IV fibers. An enhancement of responses to passive movements of the joint (sensitization) occurred in 37% of group III and 19% of group IV afferents. In summary, 37.5% of the low-threshold and 50% of the high-threshold fibers proved to be sensitive to PDBu. Most of the PDBu-positive units responded also to bradykinin, whereas only a few PDBu-positive units were sensitive to prostaglandin I2 and E2. We conclude from these results that, in a distinct population of slowly conducting joint afferents, protein kinase C is likely to be involved in the process of transduction. Thus, pain and hyperalgesia may be mediated at least partly by intracellular mechanisms that are linked to protein kinase C.
Schepelmann
K
K
Physiologisches Institut, Universität Würzburg, Federal Republic of Germany.
Messlinger
K
K
Schmidt
R F
RF
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002415:Cats; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006614:Hindlimb / Q000502:physiology; D007719:Knee Joint / Q000294:innervation*; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D003995:Dibutyryl Cyclic GMP; D015240:Phorbol 12,13-Dibutyrate; D003994:Bucladesine; D011464:Epoprostenol; D011493:Protein Kinase C; D015232:Dinoprostone; D001920:Bradykinin