PARTICIPATION OF CENTRAL DESCENDING NOCICEPTIVE FACILITATORY SYSTEMS IN SECONDARY HYPERALGESIA PRODUCED BY MUSTARD OIL

The present series of experiments were designed to examine a potential role for central descending pain facilitatory systems in mediating se condary hyperalgesia produced by topical application of mustard oil an d measuring the nociceptive tail-flick reflex in awake rats. Topical a pplication of mustard oil (100%) to the lateral surface of the hind le g produced a facilitation of the tail-flick reflex that was significan tly reduced in spinal transected animals. Mustard oil hyperalgesia was also inhibited in animals that had received electrolytic lesions in t he rostral ventromedial medulla (RVM). Intrathecal (i.t.) administrati on of the non-selective cholecystokinin (CCK) receptor antagonist prog lumide (10 mu g) prior to mustard oil application completely blocked b oth the lesser and greater hyperalgesic responses observed in spinal t ransected and normal animals, respectively, and produced an inhibition of the tail-nick reflex in normal animals. Administration of the sele ctive CCKB receptor antagonist L-365260 i.t. dose-dependently inhibite d mustard oil hyperalgesia (ID50 = 364 ng) at doses approximately 5-fo ld less than the CCKA receptor antagonist devazepide (ID50 = 1760 ng). Similar to spinal proglumide, microinjection of the neurotensin antag onist SR48692 (3.5 mu g) into the RVM blocked mustard oil hyperalgesia and inhibited the tail-flick reflex. These data suggest that secondar y hyperalgesia produced by mustard oil is mediated largely by a centra l, centrifugal descending pain facilitatory system which involves neur otensin in the RVM and spinal CCK (via CCKB receptors). The inhibition of the tail-flick reflex produced by mustard oil following spinal or supraspinal administration of receptor antagonists suggests concurrent activation of central descending facilitatory and inhibitory systems.