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.
Physiologisches Institut, Universität Würzburg, Federal Republic of Germany.
K
K
Schepelmann
K
K
Messlinger
R F
RF
Schmidt
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