Stress activates multiple neural pathways and
neurotransmitters that often suppress pain perception, the phenomenon called stress-induced
analgesia (SIA).
Orexin neurons from the lateral hypothalamus project to entire brain structures such as the hippocampus. The present study examined this hypothesis that orexinergic receptors in the CA1 region of the hippocampus may play a modulatory role in the development of SIA in
formalin test as an animal model of persistent inflammatory
pain. One hundred-two adult male Wistar rats were administered with intra-CA1 orexin-1 receptor (OX1r) antagonist, SB334867, at the doses of 3, 10, 30, and 100 nmol or
TCS OX2 29 as orexin-2 receptor (OX2r) antagonist at the doses of 1, 3, 10, and 30 nmol. Five min later, rats were exposed to forced swim stress (FSS) for a 6-min period. Then,
pain-related behaviors induced by
formalin injection were measured at the 5-min blocks during a 60-min period of
formalin test. The current study indicated that solely stress exposure elicits antinociception in the early and late phases of the
formalin test. The FSS-induced
analgesia was prevented by intra-CA1 administration of SB334867 or
TCS OX2 29 during either phase of the
formalin test. Moreover, the contribution of the OX2r in the mediation of
analgesic effect of stress was more prominent than that of the OX1r during both phases of the
formalin test. It is suggested that OX1r and OX2r in the CA1 region of the hippocampus are involved in stress-induced
analgesia in the animal model of persistent inflammatory
pain.