Nociception and allodynia/hyperalgesia induced by intrathecal administration of fenvalerate

The intrathecal injection of fenvalerate, a sodium channel activator, at do ses of 0.01 to 3 mug, dose-dependently induced the duration of a characteri stic behavioral syndrome mainly consisting of reciprocal hind limb scratchi ng directed towards caudal parts of the body and biting or licking of the E nd legs in mice. Fenvalerate-induced behavior was inhibited by morphine (1 - 10 mg/kg, i.p.). The characteristic behavior was also inhibited by mexile tine, a sodium channel blocker; MK-801, a N-methyl-D-aspartate ion-channel blocker; and GR82334, a neurokinin-1-receptor antagonist. Calphostin C (3 p mol, i.t.), a protein kinase C inhibitor, inhibited fenvalerate-induced beh avior. On the other hand, phorbol-12, 13-dibutyrate (50 pmol,i.t.), a prote in 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/hyp eralgesia, and they suggest that tetrodotoxin-resistant sodium channels may play an important role in this effect.