Copaifera langsdorffii Desf. tree oleoresin-induced antinociception recruits µ1- and κ -opioid receptors in the ventrolateral columns of the periaqueductal gray matter.

Popular medicine has been using oleoresin from several species of copaíba tree for the treatment of various diseases and its clinical administration potentially causes antinociception. Electrical stimulation of ventrolateral (vlPAG) and dorsolateral (dlPAG) columns of the periaqueductal gray matter also causes antinociception. The aim this study was to verify the antinociceptive effect of oleoresin extracted from Copaifera langsdorffii tree and to test the hypothesis that oleoresin-induced antinociception is mediated by µ1- and κ-opioid receptors in the vlPAG and dlPAG. Nociceptive thresholds were determined by the tail-flick test in Wistar rats. The copaíba tree oleoresin was administered at different doses (50, 100 and 200 mg/kg) through the gavage technique. After the specification of the most effective dose of copaíba tree oleoresin (200 mg/kg), rats were pretreated with either the µ1-opioid receptor selective antagonist naloxonazine (at 0.05, 0.5 and 5 µg/ 0.2 µl in vlPAG, and 5 µg/ 0.2 µl in dlPAG) or the κ-opioid receptor selective antagonist nor-binaltorphimine (at 1, 3 and 9 nmol/ 0.2 µl in vlPAG, and 9 nmol/ 0.2 µl in dlPAG). The blockade of µ1 and κ opioid receptors of vlPAG decreased the antinociception produced by copaíba tree oleoresin. However, the blockade of these receptors in dlPAG did not alter copaíba tree oleoresin-induced antinociception. These data suggest that vlPAG µ1 and κ opioid receptors are critically recruited in the antinociceptive effect produced by oleoresin extracted from Copaifera langsdorffii.

The blockade of µ­opioid receptors in the lateral hypothalamus enhances panic attack­like behaviour and diminishes defensive antinociception.

The lateral hypothalamus (LH) sends neural pathways to structures involved on predator­related defensive behaviours, escape and antinociception. The aim of this study was to investigate the role played by µ-opioid receptors located on LH neurons in defensive behaviour and unconditioned fear­induced antinociception elicited by electric stimulation of LH. To achieve the goals, the µ1-opioid receptor selective antagonist naloxonazine was administered at different concentrations in the LH, and the defensive behaviour and fear­induced antinociception elicited by electrical stimulation of LH were evaluated. The electrical stimulation of LH caused escape behaviour followed by defensive antinociception. Microinjections of naloxonazine in a concentration of 5.0 µg/0.2 µL in the LH decreased the aversive stimulus­induced escape behaviour thresholds, but diminished defensive antinociception. These findings suggest that µ-opioid receptors of LH can be critical to panic attack­related symptoms and facilitate the unconditioned fear­induced antinociception produced by LH neurons activation.