Effect of diabetes on bradykinin-induced thermal hyperalgesia in mice.
To investigate the role of protein kinase C in the attenuation of bradykinin-induced thermal hyperalgesia in diabetic mice, we examined the effects of a protein kinase C activator or inhibitor on the i.t. bradykinin-induced hyperalgesia in diabetic and non-diabetic mice. Intrathecal injection of bradykinin caused a transient antinociceptive effect, which diminished within 30 min, and then produced a thermal hyperalgesia, which lasted about 120 min, in non-diabetic mice. Although the duration of the antinociceptive phase was longer in diabetic mice than in non-diabetic mice, the hyperalgesic response was not observed in diabetic mice. The bradykinin-induced hyperalgesia was dose-dependently and significantly enhanced by pretreatment with calphostin C (0.3 to 3 pmol, i.t.), a specific protein kinase C inhibitor, in diabetic mice. However, calphostin C (3 pmol, i.t.) had no significant effect on bradykinin-induced hyperalgesia in non-diabetic mice. On the other hand, pretreatment with phorbol-12, 13-dibutyrate (12.5 to 50 pmol, i.t.), a protein kinase C activator, significantly and dose-dependently reduced bradykinin-induced hyperalgesia in non-diabetic mice. However, phorbol-12, 13-dibutyrate (50 pmol, i.t. ) had no significant effect on bradykinin-induced hyperalgesia in diabetic mice. These results suggest that the change in bradykinin-induced thermal hyperalgesia 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.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, Japan. kamei@hoshi.ac.jp
Ohsawa
M
M
Hitosugi
H
H
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009281:Naphthalenes / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D015240:Phorbol 12,13-Dibutyrate; C065679:icatibant; D011493:Protein Kinase C; C058819:calphostin C; D001920:Bradykinin