Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK1 receptors

摘要

Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P-containing neurons by using i.t. injection of tachykinin neurokinin (NK)1 receptor antagonists and substance P (SP) antiserum.Nociceptin-induced behavioural response was evoked significantly 5–10 min after i.t. injection and reached a maximum at 10–15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 0.375–30.0 fmol, and the maximum effect was observed at 3.0 fmol.The behavioural response elicited by nociceptin (3.0 fmol) was dose-dependently inhibited by intraperitoneal (i.p.) administration of morphine.The NK1 receptor antagonists, CP-96,345, CP-99,994 and sendide, inhibited nociceptin-induced behavioural response in a dose-dependent manner. A significant antagonistic effect of [D-Phe7, D-His9]SP (6–11), a selective antagonist for SP receptors, was observed against nociceptin-induced response. The NK2 receptor antagonist, MEN-10376, had no effect on the response elicited by nociceptin.Pretreatment with SP antiserum resulted in a significant reduction of the response to nociceptin. No significant reduction of nociceptin-induced response was detected in mice pretreated with NKA antiserum.The N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK-801) and D(−)-2-amino-5-phosphonovaleric acid (APV) (D-APV), and L-NG-nitro arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, failed to inhibit nociceptin-induced behavioural response.The present results suggest that SP-containing neurons in the mouse spinal cord may be involved in elicitation of scratching, biting and licking behaviour following i.t. injection of nociceptin.