Nociceptive behavior induced by poly- l-lysine and other basic compounds involves the spinal NMDA receptors

Abstract

We have previously shown that spermine, a basic polyamine, and big dynorphin, a basic polypeptide, induce nociceptive behavior if injected intrathecally (i.t.) in mice (see [Pain 86 (2000) 55–61] and [Brain Res. 952 (2002) 7–14]). This suggests that other basic molecules might have the same effects. Here, i.t. administration of poly- l-lysine (12 and 36 pg) to mice was found to produce the same characteristic behavioral response, biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank, which peaked at 0–10 min after injection. The behavior induced by poly- l-lysine (12 pg) was dose-dependently inhibited by intraperitoneal injection of morphine (0.25–4 mg/kg) and also dose-dependently, by i.t. co-administration of d-(−)-2-amino-5-phosphonovaleric acid ( d-APV) (1–4 nmol), a competitive N-methyl- d-aspartate (NMDA) receptor antagonist, (5 R,10 S)-(+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a, d]cycloheptene-5,10-imine hydrogen maleate (MK-801) (0.0156–4 nmol), an NMDA ion-channel blocker, and ifenprodil (2–8 nmol), an antagonist of the polyamine recognition site and the NR2B-containing NMDA receptor subtype. On the other hand, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA glutamate receptor antagonist, 7-chlorokynurenic acid, a competitive antagonist of the glycine recognition site on the NMDA receptor ion-channel complex, [ d-Phe 7, d-His 9]-substance P (6-11), a specific antagonist for substance P (NK1) receptors, or MEN-10,376, a tachykinin NK2 receptor antagonist, had no effect. These results confirm the observations obtained with other basic molecules and suggest that the behavior induced by poly- l-lysine is mediated through the activation of the NMDA receptor ion-channel complex acting either on the polyamine recognition site or on the NR2B subunit.