Orexin A induced antinociception in the ventral tegmental area involves D1 and D2 receptors in the nucleus accumbens

Blockade of D1-like dopamine receptors within the ventral tegmental area and nucleus accumbens attenuates antinociceptive responses induced by chemical stimulation of the lateral hypothalamus

“…We previously showed that chemical stimulation of the LH by the injection of carbachol induces antinociception and VTA and NAc orexin receptors are involved in this antinociception [4,26]. In addition, another study in our lab revealed that intra-accumbal administration of D1-and/or D2-like receptor antagonists decreased the antinociceptive effects of intra-VTA orexin-A injection and administration of D2-like receptor antagonist had a more remarkable effect than D1-like receptor antagonist [30]. In that study, we administrated exogenous orexin into the VTA which resulted in the stimulation of all of the orexin receptors in this area.…”

“…Microinjection of D1-and D2-like receptor antagonists into the NAc could prevent the antinociceptive effects induced by morphine in the tail flick test [23]. Additionally, Yazdi-Ravandi et al showed that intra-accumbal injection of D1-and/or D2-like receptor antag- onists decreased the antinociceptive effects of intra-VTA orexin-A injection in tail-flick test and administration of D2-like receptor antagonist had a more considerable effect than D1-like receptor antagonist [30]. However, in the current study, we triggered orexin receptors in the VTA and NAc by release of the endogenous orexin (LH mostly sends orexinergic projects to the VTA and NAc, and results in the release of endogenous orexin in these areas) which led to the stimulation of orexin receptors located in these synapses not all of the orexin receptors in these regions.…”

“…Numerous studies clarified that the orexinergic projections from the LH to the VTA and NAc are directly/indirectly involved in antinociception induced by chemical stimulation of the LH [4,23,25,28]. In addition, there is a functional interplay between the orexinergic system and mesolimbic dopaminergic pathway [4,21,25,30] and it was shown that orexinergic projections from the LH to the VTA stimulate the release of dopamine in mesolimbic areas such as the NAc [21]. Dopaminergic neurons in the VTA are involved in both endogenous and morphineinduced antinociception.…”

Affective Circuitry Alterations in Patients with Trigeminal Neuralgia

“…It is strongly implicated in the processing of appetitive and aversive stimuli (Hayes et al, 2014 ), and the VTA is important in human pain processing (Fairhurst et al, 2007 ; Hayes and Northoff, 2012 ). Animal studies have identified a host of neurochemical factors involved in regulating the nociceptive response within the VTA, including a complex involvement of orexin, opioids, and dopamine (Yazdi-Ravandi et al, 2014 ; Hipolito et al, 2015 ). Increased VTA microglial activation is associated with chronic neuropathic pain (Taylor et al, 2015 ), and is one possible explanation for the altered dMRI metrics in the present study, as increased microglial activation reflects local inflammation which may lead to disruptions in water diffusivity, decreased FA, and increased MD and RD (Alexander et al, 2007 ; Po et al, 2012 ).…”

Odour-induced analgesia mediated by hypothalamic orexin neurons in mice

“…Orexin neurons can also induce anti-nociception by modulating the VTA-nucleus accumbens (NAc) pathway. Intra-VTA administration of orexin-A induces anti-nociception in a dose-dependent manner50. Moreover, intra-VTA administration of an orexin-1 receptor antagonist prevents lateral hypothalamus stimulation-induced anti-nociception51.…”