μ but not δ and κ opioid receptor involvement in ventrolateral orbital cortex opioid-evoked antinociception in formalin test rats

Abstract

The present study was designed to investigate the roles of different subtypes of opioid receptors in ventrolateral orbital cortex (VLO) opioid-evoked antinociception in formalin test by using an automatic detection system for recording the nociceptive behavior (agitation) and a manual method for detecting the duration of licking the injected paw in the conscious rat. Formalin (5%, 50 μl) s.c. injected into the hindpaw produced a biphasic agitation response or lengthening duration of licking. Morphine (5 μg) microinjected unilaterally into VLO significantly inhibited the agitation response and the licking time, and these effects were blocked by pre-administration of the non-selective opioid receptor antagonist naloxone (1.0 μg) into the same site. Microinjection of endomorphin-1 (5 μg), a selective μ-receptor agonist, and [ d-Ala 2, d-Leu 5]-enkephalin (DADLE, 10 μg), a δ-/μ-receptor agonist also inhibited the nociceptive behaviors, and both the effects were blocked by selective μ-receptor antagonist β-funaltrexamine hydrochloride (β-FNA; 3.75 μg), but the DADLE-evoked inhibition was not influenced by the selective δ-receptor antagonist naltrindole (5 μg). Microinjection of selective κ-receptor agonist (±)- trans-U-50488 methanesulfonate salt (1.5 μg) failed to alter the nociceptive behaviors induced by formalin injection. The β-FNA and naloxone applied into VLO and morphine into the adjacent regions ventral and dorsal to VLO had no effect on the formalin-evoked nociceptive behaviors. These results suggest that μ- but not δ- or κ-opioid receptor is involved in the VLO opioid-evoked antinociception in formalin test rat.