Intra-CA1 injection of orexin receptors antagonism attenuates the stress-induced analgesia in a rat acute pain model

Contribution of the intra-hippocampal orexin system in the regulation of restraint stress response to pain-related behaviors in the formalin test

“…In the present study, SIA was blocked by the intra-CA1 injection of OX1r and OX2r antagonists in both phases of the formalin test. These results are consistent with previous findings showing that swimming stress affects both phases of formalin-induced pain, and SIA is blocked by the intra-CA1 injection of OX1r and OX2r antagonists in both phases of the formalin test (Ghalebandi et al ., 2022). In the present study, the maximal dose of SB334867 and TCS OX2 29 alone were injected into the CA1 region and were shown to have no significant effect on the formalin test’s early and late phases.…”

“…These results are consistent with other studies that reported that foot electric shock stress activates orexinergic neurons and induces antinociception (Watanabe et al ., 2005). On the other hand, our studies show that orexin receptors in different brain areas modulate antinociception caused by various stresses, such as the stress of forced swimming in acute and chronic pain (Heidari-Oranjaghi et al ., 2012; Ghalebandi et al ., 2022). Hypothalamic orexin neurons have been shown to activate and release orexins (Ho et al ., 2011).…”

“…Work by others has shown that the hippocampus receives orexinergic projections from the hypothalamus, and orexin receptors are excited in different hippocampus areas, such as the CA1 (Boss and Roch, 2015). There is a substantial body of evidence suggesting that the hippocampal formation plays a role in nociception (Sargin, 2019; Ghalebandi et al ., 2022). Additionally, certain neural populations within the dorsal hippocampal Cornu Ammonis 1 (CA1) region have been observed to respond to persistent noxious stimuli.…”

“…Our recent studies showed that orexin receptors in the CA1 modulate formalin-induced orofacial pain and reduce acute stress-induced nociceptive responses in the tail-flick test (Haghparast et al ., 2018; Ghalebandi et al ., 2022). In 2017, Chen showed that orexin-A exerts excitatory effects on CA1 region neurons through OX1 receptors (Chen et al ., 2017).…”

The Underlying Mechanisms of Sleep Deprivation Exacerbating Neuropathic Pain

“…The wakefulness-promoting effects of orexin have been validated in several multicenter, double-blind, randomized, placebo-controlled studies [115][116][117][118] and have recently been approved by the FDA for the treatment of adults who have insomnia. 119 Orexins are also associated with brain regions that regulate pain; 120 for example, orexins in the ventral tegmental area are associated with injurious responses. 121 Exogenously administered orexins have been shown to have analgesic effects in animal models.…”