INVOLVEMENT OF SPINAL CHOLECYSTOKININ(B) RECEPTORS IN MEDIATING NEUROTENSIN HYPERALGESIA FROM THE MEDULLARY NUCLEUS RAPHE MAGNUS IN THE RAT

Neurotensin microinjection into the medullary nucleus raphe magnus (RM g) has been shown to both inhibit and facilitate the spinal nociceptiv e tail-flick reflex in a dose-dependent manner. Our study was designed to determine a potential involvement of spinal cholecystokinin octape ptide (CCK) in mediating neurotensin hyperalgesia from the RMg. Microi njection of neurotensin (50 ng) into the RMg of awake rats produced a facilitation of the tail-flick reflex that was completely inhibited by intrathecal (i.t.) administration of the nonselective CCK receptor an tagonist proglumide (100 ng). Conversely, injection of a greater dose of neurotensin (5 mu g) into the RMg produced an inhibition of the tai l-flick reflex that was enhanced by i.t. proglumide. Intrathecal admin istration of the selective CCKB receptor antagonist L-365260 dose-depe ndently inhibited neurotensin hyperalgesia from the RMg (ID50 = 0.42 n g) at doses approximately 1000-fold less than that observed with the s elective CCKA receptor antagonist devazepide (ID50 = 646 ng). Injectio n of CCK alone i.t. produced a biphasic response an the tail-flick ref lex as lesser doses (0.1-0.3 ng) inhibited the reflex although greater doses (30-100 ng) facilitated it. Similar to supraspinal neurotensin hyperalgesia, the hyperalgesia observed with i.t. CCK (30 ng) was inhi bited by i.t. L-365260 (ID50 = 0.59 ng) at doses approximately 1000-fo ld less than that observed with i.t. devazepide (ID50 = 630 ng). These data indicate that spinal CCK can both inhibit and facilitate spinal nociceptive responses. The facilitation of nociception observed with s pinal CCK appears to involve CCKB receptors, which is consistent with the data in our study suggesting that spinal CCKB receptors mediate ne urotensin hyperalgesia from the RMg via descending neuronal projection s.