Modification of the fenvalerate-induced nociceptive response in mice by diabetes.
We examined the effect of diabetes on the fenvalerate-induced nociceptive response in mice. The intrathecal (i.t.) or intraplantar (i.pl.) injection of fenvalerate, a sodium channel activator, induced a characteristic behavioral syndrome mainly consisting of reciprocal hind limb scratching directed towards caudal parts of the body and biting or licking of the hind legs in both non-diabetic and diabetic mice. However, the intensity of such fenvalerate-induced nociceptive responses was significantly greater in diabetic mice than in non-diabetic mice. Calphostin C (3 pmol, i.t.), a selective protein kinase C inhibitor, significantly inhibited intrathecal fenvalerate-induced nociceptive behavior with a rightward shift of the dose-response curve for fenvalerate-induced nociceptive behavior to the level those observed in non-diabetic mice. On the other hand, when non-diabetic mice were pretreated with phorbol-12, 13-dibutyrate (50 pmol, i.t.), the dose-response curve for intrathecal fenvalerate-induced nociceptive behavior was shifted leftward to the level those observed in diabetic mice. These results suggest that the sensitization of sodium channels, probably tetrodotoxin-resistant (TTX-R) sodium channels, by the long-term activation of protein kinase C may play an important role in the enhancement of the duration of fenvalerate-induced nociceptive behavior in diabetic mice.
Kamei
Junzo
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-Chome, Shinagawa-ku, Tokyo 142-8501, Japan. kamei@hoshi.ac.jp
Iguchi
Emiko
E
Sasaki
Mitsumasa
M
Zushida
Ko
K
Morita
Kayo
K
Tanaka
Shun-ichi
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D008801:Mexiletine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009281:Naphthalenes / Q000494:pharmacology; D009570:Nitriles; D010147:Pain Measurement / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011722:Pyrethrins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects; D013311:Streptozocin
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; D008801:Mexiletine; D015240:Phorbol 12,13-Dibutyrate; D013311:Streptozocin; D011493:Protein Kinase C; C058819:calphostin C; C017690:fenvalerate