Nociceptin‐induced scratching, biting and licking in mice: involvement of spinal NK 1 receptors

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 NK 1 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 ‐Phe 7 , D ‐His 9 ]SP (6–11), a selective antagonist for SP receptors, was observed against nociceptin‐induced response. The NK 2 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 ‐N G ‐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.British Journal of Pharmacology (1999) 127 , 1712–1718; doi: 10.1038/sj.bjp.0702698