Role of the orexinergic system in
pain modulation is well studied and involvement of the spinal orexin-1 receptors is well documented. In this study, we examined role of the spinal orexin-2 receptors in modulation of inflammatory
pain in rat. Fifty-one adult male Wistar rats were implanted unilaterally with a guide
cannula into the LH and intrathecal tubing in the lumbar space between L4 and L5. Chemical stimulation of LH by
carbachol (250 nM/0.5 µL saline) induced remarkable
analgesia during the two phases of
formalin test and Intrathecal administration of different doses of
TCS OX2 29 (10, 30 and 100 µM/ 0.5 µL
DMSO) prior to LH stimulation, dose-dependently antagonized the antinociceptive effect of the LH-stimulation during the two phases of
formalin test. The effect size of the
TCS OX2 29 was η2 = 0.47 and η2 = 0. 87 for the early and late phases of the test, respectively. Also, intrathecal administration of
TCS OX2 29 alone (without stimulation of the LH) had no significant effect on
formalin induced
pain-related behaviors. Our results showed that spinal orexin-2 receptors are involved in modulation of the LH-stimulation induced
analgesia in a persistent inflammatory
pain model. These findings may suggest spinal orexin-2 receptors in particular and the
orexin system in general as a useful therapeutic target for treatment of chronic pains.