Modulation of the formalin-induced nociceptive response by diabetes: possible involvement of protein kinase C.
Injection of formalin into the hind paw of mice produced a biphasic nociceptive response consisting of immediate (first-phase) and tonic (second-phase) components. Although the duration of the first-phase response was significantly longer in diabetic mice than in nondiabetic mice, the second phase was significantly shorter in diabetic mice. The first-phase response was dose-dependently and significantly reduced by pretreatment with calphostin C (0.3 to 3 pmol, i.t.), a specific protein kinase C inhibitor, in diabetic mice. The second-phase response was markedly increased when diabetic mice were pretreated with calphostin C. However, calphostin C (3 nmol, i. t.) had no significant effect on either the first-phase or second-phase response in nondiabetic mice. On the other hand, pretreatment with phorbol-12,13-dibutyrate (50 pmol, i.t.), a protein kinase C activator, significantly enhanced the first-phase response in nondiabetic mice. These results suggest that the change in the formalin-induced nociceptive response in diabetic mice may be due, at least in part, to the modification of nociceptive transmission in the spinal cord by the activation of protein kinase C.
Ohsawa
M
M
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142, Japan.
Kashiwazaki
T
T
Kamei
J
J
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005557:Formaldehyde / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000008:administration & dosage / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*
D005557:Formaldehyde; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C