Orexins are produced in the restricted regions of the lateral hypothalamus (LH). However, orexinergic receptors and projections are localized in wide regions like nucleus accumbens, ventral tegmental area, periaqueductal gray area and spinal cord which are involved in the
pain modulation. This study was carried out to investigate the effects of intrathecal administration of orexin-1 receptor antagonist (SB-334867) in the spinal antinociception induced by intra-LH administration of
carbachol (
cholinergic receptor agonist) in both early and late phases of
pain related behaviors in
formalin test. In this study,
pain-related behaviors (
pain scores) were evaluated using the
formalin test during 5-min block intervals for a 60-min period in seventy male Wistar rats were given
SB-334867 (3, 10, 30 and 100 μM/10 μl) or vehicle (
DMSO 12%; 10 μl) intrathecally following intra-LH administration of
carbachol (250 nM/rat). Our data showed that intra-LH injection of
carbachol attenuated the
formalin-induced biphasic
pain responses, and intrathecal administration of
SB-334867 dose-dependently decreased LH stimulation-induced antinociceptive responses during both phases. Moreover, administration of different doses of
SB-334867 during the early phase were more effective than those during the late phase. The antinociceptive role of orexinergic system in the
formalin test through a neural pathway from the LH to the spinal cord provides evidence that
orexins can be useful in therapeutic targets for
pain relief.