Intra-accumbal Orexin-1 Receptors are Involved in Antinociception Induced by Stimulation of the Lateral Hypothalamus in the Formalin Test as an Animal Model of Persistent Inflammatory Pain.

Abstract

Orexin, mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), plays an important role in pain modulation. Moreover, it is shown that the nucleus accumbens (NAc) is one of the important areas involved in this modulation. Orexin-1 (OX1) and orexin-2 (OX2) receptors are densely distributed in the NAc. The study investigated the involvement of OX1 receptors in the NAc on antinociception induced by intra-LH administration of carbachol in formalin test. Rats were unilaterally implanted by two separate cannulae into the LH and NAc. Different doses of SB334867, as an OX1 receptor antagonist, were microinjected into the NAc (1, 3 and 10 nM/0.5 µL DMSO) prior to intra-LH carbachol injection (250 nM/0.5 µL saline). Formalin test was applied as an animal model of persistent inflammatory pain. The animals received a subcutaneous injection of formalin into the hind paw, 5 min after SB334867 administration. Pain scores were calculated at 5-min blocks for a 60-min test period. Results showed that the administration of SB334867 into the NAc decreased LH chemical stimulation-induced antinociception dose-dependently in early and second phase of formalin test. Our findings showed that OX1 receptors in the NAc may be involved in modulation of inflammatory pain.