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.
Copyright 1998 Elsevier Science B.V.