Blockade of the orexin receptors in the ventral tegmental area could attenuate the stress-induced analgesia: A behavioral and molecular study

Askari, Kobra; Oryan, Shahrbanoo; Eidi, Akram; Zaringhalam, Jalal; Haghparast, Abbas

doi:10.1016/j.pnpbp.2022.110639

Cited by 6 publications

(1 citation statement)

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“…Besides, several studies have already exhibited that stressful stimuli promote changes in the activity of several supraspinal structures, including VTA and substantia nigra dopaminergic neurons, projecting to widespread brain areas, resulting in an antinociceptive response (Mitsi and Zachariou, 2016). Accordingly, it has already been shown that the blockade of both orexin receptors (excitatory neurotransmitter receptors) within the VTA (the major place of origin of dopaminergic neurons) attenuates antinociceptive responses induced by either physical or psychological stressors (Askari et al, 2021(Askari et al, , 2023. Various pain perception-involved neurotransmitters, however, have already been suggested as inflammatory and noninflammatory mediators (Yam et al, 2018), and this series of lab studies showed that both D1R and D2R within the DG played a significant role in SIA in the acute thermal pain model as well as inflammatory pain model.…”

Section: Discussionmentioning

confidence: 99%

D2-like dopamine receptors blockade within the dentate gyrus shows a greater effect on stress-induced analgesia in the tail-flick test compared to D1-like dopamine receptors

Golmohammadi,

Shirmohammadi,

Mazaheri

et al. 2024

Behavioural Pharmacology

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Introduction Acute stress, as a protective mechanism to respond to an aversive stimulus, can often be accompanied by suppressing pain perception via promoting consistent burst firing of dopamine neurons. Besides, sensitive and advanced research techniques led to the recognition of the mesohippocampal dopaminergic terminals, particularly in the hippocampal dentate gyrus (DG). Moreover, previous studies have shown that dopamine receptors within the hippocampal DG play a critical role in induced antinociceptive responses by forced swim stress (FSS) in the presence of inflammatory pain. Since different pain states can trigger various mechanisms and transmitter systems, the present experiments aimed to investigate whether dopaminergic receptors within the DG have the same role in the presence of acute thermal pain. Methods Ninety-seven adult male albino Wistar rats underwent stereotaxic surgery, and a stainless steel guide cannula was unilaterally implanted 1 mm above the DG. Different doses of SCH23390 or sulpiride as D1- and D2-like dopamine receptor antagonists were microinjected into the DG 5–10 min before exposure to FSS, and 5 min after FSS exposure, the tail-flick test evaluated the effect of stress on the nociceptive response at the time-set intervals. Results The results demonstrated that exposure to FSS could significantly increase the acute pain perception threshold, while intra-DG administration of SCH23390 and sulpiride reduced the antinociceptive effect of FSS in the tail-flick test. Discussion Additionally, it seems the D2-like dopamine receptor within the DG plays a more prominent role in FSS-induced analgesia in the acute pain model.

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