Role of orexin receptors within the dentate gyrus of the hippocampus in antinociception induced by chemical stimulation of the lateral hypothalamus in the tail-flick test as a model of acute pain in rats

Brojeni, Masoud Shareghi; Rashvand, Mina; Haghparast, Abbas

doi:10.1016/j.physbeh.2019.112595

Cited by 14 publications

(11 citation statements)

References 44 publications

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“…Accordingly, stress seems to exert its antinociceptive effects by activating the orexinergic neurons and affecting synaptic efficacy in the hippocampus. Furthermore, inconsistent with previous studies (Brojeni et al, 2019;Rasouli et al, 2020), the present findings revealed infusions of OX1r and OX2r antagonists alone into the dentate gyrus, and so, these orexin receptors in this region do not appear to mediate antinociception by themselves.…”

Section: Discussioncontrasting

confidence: 99%

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

Bolouri-Roudsari,

Baghani,

Askari

et al. 2023

Behavioural Pharmacology

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The stressful experiences, by triggering a cascade of hormonal and neural changes, can produce antinociception commonly referred to as stress-induced antinociception (SIA). Orexin neuropeptides have an essential role in stress responses and pain modulation. The dentate gyrus receives orexinergic projections and has been shown to be involved in pain processing. The current study investigated the possible role of orexin-1 and orexin-2 receptors (OX1r and OX2r, respectively) within the dentate gyrus in SIA in a rat model of formalin-induced pain behavior in one hind paw. Male Wistar rats weighing 230–250 g underwent stereotaxic surgery and a cannula was implanted in their brains, above the dentate gyrus region. Either SB334867 or TCS OX2 29 (OX1r and OX2r antagonists, respectively) was microinjected into the dentate gyrus region at a range of doses at 1, 3, 10, and 30 nmol (control group received DMSO 12% as vehicle), 5 min before the forced swim stress (FSS) exposure. The formalin test was performed to assess pain-related behaviors. The results indicated that FSS exposure relieves pain-related behavior in the early and late phases of the formalin test. Blockade of intra-dentate gyrus OX1 or OX2 receptors reduced the antinociceptive responses induced by FSS in the formalin test, with more impact during the late phase. Our findings support the potential role of intra-dentate gyrus orexin receptors as target sites of orexin neurons in painful and stressful situations. Therefore, understanding the exact mechanisms of SIA and the role of the orexinergic system in this phenomenon can lead to identifying the strategies to guide future research and offer a new approach to discovering new pain therapeutic agents.

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Section: Discussioncontrasting

confidence: 99%

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

Bolouri-Roudsari,

Baghani,

Askari

et al. 2023

Behavioural Pharmacology

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“…So, LH projections to the lateral habenula regulate aversion but not nociception (Siemian et al , 2021). In this respect, it has been shown that the LH-DG neural circuitry participates in pain modulation via the LHs’ projections to the DG region in multiple animal models of acute and chronic pain (Brojeni et al , 2019; Khaleghzadeh-Ahangar et al , 2021; Torkamand et al , 2021). According to the results of immunohistochemistry studies, the c-fos expression as a sensitive and reliable marker of neuronal activity increased in the hippocampal DG and CA3 regions at two hours following subcutaneous injection of formalin in rats (Ceccarelli et al , 1999).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, it has been demonstrated that LH stimulation attenuated tonic pain through the dopaminergic receptors within the ventral tegmental area (VTA) following the rat’s paw formalin injection (Siahposht-Khachaki et al , 2021). Besides, chemical stimulation of LH could attenuate acute pain via orexin receptors within the dentate gyrus (DG) of the hippocampus (Brojeni et al , 2019). LH stimulation could also reduce hyperalgesia through orexin-A neurons in an animal model of neuropathic pain (Wardach et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

Involvement of dopaminergic system in the dentate gyrus of the hippocampus in modulating the orofacial pain-related behaviors in the rats

Haghparast

Yousefpour

Rashvand

et al. 2023

Behavioural Pharmacology

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Chemical stimulation of the lateral hypothalamus (LH) induces analgesia by forming neural circuitries with multiple brain regions. The involvement of hippocampal dopaminergic receptors in the LH stimulation-induced antinociception in specific pain models in animals has been documented. However, because the neural circuitries involved in the mediation of orofacial pain are not the same as those that mediate the other types of pain, the present study aims to detect the role of dopamine receptors within the dentate gyrus (DG) in the antinociceptive responses induced by LH stimulation in an animal model of orofacial pain. Male Wistar rats (220–250 g) were implanted with two separate cannulae into the LH and DG on the same side. D1- or D2-like dopamine receptor antagonist, SCH23390, or sulpiride (0.25, 1, and 4 μg) were microinjected into the DG, five minutes before intra-LH injection of carbachol (250 nM). The animals were then injected with formalin 1% (50 μL; sc) into the upper lip lateral to the nose and subjected to the orofacial formalin test. Intra-DG administration of SCH23390 or sulpiride attenuated the antinociceptive responses induced by intra-LH microinjection of carbachol during the orofacial formalin test. The findings of the current study suggest that chemical stimulation of the LH modulates orofacial pain, possibly through activation of the DG dopaminergic neurons. Due to the high incidence and prevalence of orofacial pain in the general population, understanding how such neuronal circuitry modulates nociceptive processing will advance the search for novel therapeutics.

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Section: Discussionmentioning

confidence: 99%

Involvement of Dopaminergic System in the Dentate Gyrus of the Hippocampus in Modulating the Orofacial Pain-Related Behaviors in the Rats

Haghparast¹,

Yousefpour²,

Rashvand³

et al. 2022

BCN

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Chemical stimulation of the lateral hypothalamus (LH) induces analgesia by formation neural circuitries with multiple brain regions. The involvement of hippocampal dopaminergic receptors in the LH stimulation-induced antinociception in certain animal models of pain has been documented, however, considering the fact that the neural circuitries involved in the mediation of orofacial pain are not the same as those that mediate the other types of pain, the present study aims to detect the role of dopamine receptors within the dentate gyrus (DG) in the antinociceptive responses induced by LH stimulation in an animal model of orofacial pain. Male Wistar rats (220-250 g) were implanted with two separate cannulae into the LH and DG on the same side. D1- or D2-like dopamine receptor antagonist, SCH23390 or Sulpiride (0.25, 1, and 4 μg) were microinjected into the DG, five minutes prior to intra-LH injection of carbachol (250 nM). The animals were then injected with formalin 1% (50 μl; sc) into the upper lip lateral to the nose and subjected to the orofacial formalin test. Intra-DG administration of SCH23390 or Sulpiride attenuated the antinociceptive responses induced by intra-LH microinjection of carbachol during orofacial formalin test. The findings of the current study suggest that chemical stimulation of the LH modulates the orofacial pain possibly through activation of the DG dopaminergic neurons. Due to the high incidence and prevalence of orofacial pain in the general population, understanding how such neuronal circuitry modulates nociceptive processing will advance the search for novel therapeutics.

show abstract

Role of orexin receptors within the dentate gyrus of the hippocampus in antinociception induced by chemical stimulation of the lateral hypothalamus in the tail-flick test as a model of acute pain in rats

Cited by 14 publications

References 44 publications

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

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

Involvement of dopaminergic system in the dentate gyrus of the hippocampus in modulating the orofacial pain-related behaviors in the rats

Involvement of Dopaminergic System in the Dentate Gyrus of the Hippocampus in Modulating the Orofacial Pain-Related Behaviors in the Rats

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