Antinociceptive effects of RB101(S), a complete inhibitor of enkephalin-catabolizing enzymes, are enhanced by (+)-HA966, a functional NMDA receptor antagonist: a c-Fos study in the rat spinal cord.

Abstract The effects of the S enantiomer of RB101, a complete inhibitor of enkephalin-catabolizing enzymes, alone or in combination with a functional NMDA receptor antagonist, (+)-HA966 were studied on the spinal c-Fos protein expression in the carrageenan model of inflammatory nociception. One hour 30 min after intraplantar carrageenan in awake rats, c-Fos immunoreactive (c-Fos-IR) nuclei were preferentially located in the laminae I–II and V–VI of the spinal dorsal horn, i.e., spinal areas containing numerous neurons responding exclusively, or not, to peripheral nociceptive stimuli. RB101(S) (5, 10, 20 and 40 mg/kg i.v.) dose-dependently reduced the total number of carrageenan-evoked c-Fos-IR nuclei ( r =0.63, P P P P P