Nociception and allodynia/hyperalgesia induced by intrathecal administration of fenvalerate.
The intrathecal injection of fenvalerate, a sodium channel activator, at doses of 0.01 to 3 microg, dose-dependently induced the duration of 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 mice. Fenvalerate-induced behavior was inhibited by morphine (1-10 mg/kg, i.p.). The characteristic behavior was also inhibited by mexiletine, a sodium channel blocker; MK-801, a N-methyl-D-aspartate ion-channel blocker; and GR82334, a neurokinin-1-receptor antagonist. Calphostin C (3 pmol, i.t.), a protein kinase C inhibitor, inhibited fenvalerate-induced behavior. On the other hand, phorbol-12, 13-dibutyrate (50 pmol, i.t.), a protein kinase C activator, markedly enhanced the fenvalerate-induced behavior. The present results also showed that fenvalerate produced thermal allodynia and hyperalgesia in the tail-flick test. Furthermore, fenvalerate-induced thermal allodynia and hyperalgesia were inhibited by the pretreatment with calphostin C. These results suggest that the intrathecal administration of fenvalerate induces a marked nociceptive response and thermal allodynia/hyperalgesia, and they suggest that tetrodotoxin-resistant sodium channels may play an important role in this effect.
Kamei
J
J
Department of Pathophysiology & Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. kamei@hoshi.ac.jp
Sasaki
M
M
Zushida
K
K
Morita
K
K
Tanaka
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced*; D007278:Injections, Spinal; D008297:Male; D008801:Mexiletine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009570:Nitriles; D010146:Pain / Q000139:chemically induced*; D010803:Physalaemin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011722:Pyrethrins / Q000008:administration & dosage / Q000494:pharmacology*
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D009570:Nitriles; D011722:Pyrethrins; C079014:GR 82334; D008801:Mexiletine; D010803:Physalaemin; D016291:Dizocilpine Maleate; D011493:Protein Kinase C; C017690:fenvalerate