Involvement of orexin-1 receptors in the ventral tegmental area and the nucleus accumbens in antinociception induced by lateral hypothalamus stimulation in rats

Previous studies have demonstrated that chemical stimulation of the lateral hypothalamus (LH) with carbachol has an important role in the induction of antinociception in tail-flick test as a model of acute pain. In this study, we tried to evaluate the involvement of orexin-1 receptors in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) on antinociceptive responses induced by LH stimulation in rats. One hundred twenty adult male albino Wistar rats weighing 200–250 g were unilaterally implanted with two separate cannulae into the LH, and VTA or NAc. Antinociceptive effects for two doses of intra-LH carbachol (125 and 250 nmol/0.5 μl saline), as a cholinergic agonist, were evaluated in this study. In another set of experiments, animals received intra-VTA or -NAc infusions of SB334867 as a selective orexin-A receptor antagonist (0.3, 1, 3 and 10 nmol/rat), just 5 min before microinjection of an effective dose of carbachol into the LH. In the tail-flick test, antinociceptive responses of drugs were obtained by tail-flick analgesiometer and represented as maximal possible effects (%MPE) at 5, 15, 30, 45 and 60 min after their administrations. The results showed that unilateral intra-LH administration of carbachol (125 and 250 nmol/rat) induced antinociception in rats (P b 0.01). There were no significant differences between the antinociceptive effects of these two doses. In the second part of our study, intra-VTA and intra-accumbal administrations of different doses of SB334867, 5 min before microinjection of carbachol, could dose-dependently prevent the development of LH stimulation-induced antinociception in rats. However, this effectwas less in the NAc. It is supposed that the orexinergic projections from the LH to the VTA and NAc are direct/indirectly involved in the antinociception induced by LH chemical stimulation, and orexin-1 receptors in the ventral tegmental area have amore substantial role in this phenomenon

The Effect of Food Deprivation on Nociception in Formalin Test and Plasma Levels of Noradrenaline and Corticosterone in Rats

Introduction: The concentration of noradrenalin and corticosterone as the two nociception modulators change after fasting or stress situation. The aim of present study was to investigate the effect of food deprivation on formalin-induced nociceptive behaviours and plasma levels of noradrenalin and corticosterone in rats. Methods: Food was withdrawn 12, 24 and 48 h prior to performing the formalin test, but water continued to be available ad libitum. The formalin solution (50 μL, 2%) was injected into plantar surface of hind paw. The nociception responses of the animals during the first phase (1-7 minutes), the inter-phase (8-14), the phase 2A (15-60) and the phase 2B (61-90) was separately evaluated. The plasma concentrations of noradrenalin and corticosterone were measured using specific ELISA and IRA kits, according to manufacturer's instructions. Results: In contrast to the increasing of 48 h food deprived animals during phase 2, the nociceptive behaviours of 12 and 24 h groups decreased through the interphase, phase 2A and phase 2B. The injection of formalin in the normal male rats significantly decreased the plasma level of noradrenalin and corticosterone. Food deprivation for 12 and 24 h increased noradrenalin level significantly in comparison with control group which has caused by fasting induced antinociceptive behaviours. There was no significant change in food deprivation for 48 h group. Food deprivation for 12, 24 and 48 h had no effect on corticosterone level in male rats. Discussion: The present study emphasizes that the acute food deprivation diminished the nociceptive behaviours in the formalin test and show a correlation with increase in plasma noradrenalin level