Orexin receptors in the CA1 region of hippocampus modulate the stress-induced antinociceptive responses in an animal model of persistent inflammatory pain

The integrative role of orexin-1 and orexin-2 receptors within the hippocampal dentate gyrus in the modulation of the stress-induced antinociception in the formalin pain test in the rat

“…In this region, immobilization stress has been shown to modify CRH and glucocorticoid receptor mRNA expression (Givalois et al, 2000;Paskitti et al, 2000) and elicit longterm depression (Xu et al, 1997). Additionally, ample evidence has indicated the involvement of different parts of the hippocampus such as CA1 and dentate gyrus regions in the SIA and pain modulation (Echeverry et al, 2002;Jiao et al, 2009;Rasouli et al, 2020;Zareie et al, 2022). Echeverry et al (2002) have suggested the involvement of dentate gyrus in the SIA.…”

“…For the first time, Watanabe et al (2005) reported that orexin-null mutant mice presented lower degree of antinociception when encountered with a stressor (Watanabe et al, 2005). It has also recently been shown that forced swim-and restraint SIA is prevented by blockade of orexin receptors in some brain regions such as periaqueductal gray, VTA, and CA1 (Lee et al, 2020;Askari et al, 2021;Zareie et al, 2022).…”

“…Consistent with these results is evidence of an antinociceptive effect for acute stress. It has been demonstrated that acute FSS potentiated the antinociceptive responses in different phases of the formalin test (Faramarzi et al ., 2016; Zareie et al ., 2022); however, some studies have shown that chronic stress causes nociceptive behaviors and elicits hyperalgesia (Scheich et al ., 2017); therefore, depending on duration and the type of stress, stress responses might be varied (Chrousos, 2009). The SIA is mediated by descending inhibitory system, so deficiency in the pain inhibitory system may disturb the SIA (Amit and Galina, 1986; Butler and Finn, 2009).…”

“…The current study also revealed that blockade of orexin-2 receptors located in the dentate gyrus region had a more pronounced effect than that of orexin-1 receptors. It has been previously shown that both intra-dentate gyrus orexin receptors play a similar role in reducing antinociceptive responses induced by drug stimulation of the lateral hypothalamus (Rasouli et al ., 2020); however, blocking the intra-CA1 orexin-2 receptors can reduce the SIA more than that of orexin-1 receptors during the formalin test (Zareie et al ., 2022). It seems that various factors such as different distribution of orexin receptors in specific brain regions, the affinity of receptors for orexin, and the experimental protocol are effective factors associated with the role of orexin receptors in pain modulation.…”

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, the OX1r antagonist, SB334867, (1, 3, 10 and 30 nmol) and the OX2r antagonist, TCS OX2 29, (1, 3, 10 and 30 nmol) (Tocris Bioscience, Bristol, UK) were prepared in a volume of 0.5 µL DMSO (12%) and injected into the CA1 region (32). All microinjections were performed using an injector connected to a 1-µl Hamilton syringe through polyethylene tubing.…”