Spinal delta-opioid receptors mediate suppression of systemic SNC80 on excitability of the flexor reflex in normal and inflamed rat

Due to low central nervous system (CNS) bioavailability of delta -opioid pe ptides. little is known about the effect of systemic administration of delt a -opioid receptor ligands. The present study examined the effect of non-pe ptidergic delta -opioid receptor agonists, (+)-4-[(alpha R)-alpha-((2 R,5R) -4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N, N-diethylbenzamide (SNC80) and (-)dibenzoyl-L-tartaric acid salt (SNC86), on the activity of alpha - motoneurons in decerebrate-spinal rats. The flexor reflex was facil itated by C-afferent conditioning inputs, shown by a decrease in mechanical threshold and increase in touch- and pinch-evoked responses. Systemic admi nistration of SNC80 (10 mu mol/kg) prevented and reversed the neuronal hype ractivity. We further examined the effect of this agonist on the hypersensi tivity of the flexor reflex induced by intraplantar injection of Freund's a djuvant. SNC80 dose-dependently (1, 3, 5 and 10 mu mol/kg) increased the me chanical threshold and decreased touch-, pinch- and A beta -afferent inputs -evoked responses. Similar effects were Seen with SNC86 (5 mu mol/kg). Pret reatment with either naloxone (20 mu mol/kg, i.p.) or (Cyclopropylmethyl)-6 ,7-dehydro-4,5 alpha -epoxy-14 beta -ethoxy-5 beta -methylindolo [2 ' ,3 ' :6 ' ,7 ' ]morphinan-3-ol hydrochloride (SH378; 5 mu mol/kg, intraarteriall y (i.a.)), a novel selective delta -opioid receptor antagonist, completely abolished the anti-hypersensitivity effect of SNC80. The effect of SNC80 re mained following intrathecal administration of mu -opioid receptor antagoni st d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; 1.5 nmol). These results indicate that systemic injection of SNC80 exerted antihypersensitivity in m odels of both acute and tonic nociception and these effects are mediated ma inly through a spinal delta -opioid mechanism. (C) 2001 Published by Elsevi er Science B.V.