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

Moradi, Marzieh; Fatahi, Zahra; Haghparast, Abbas

doi:10.1016/j.neulet.2015.05.047

Cited by 14 publications

(9 citation statements)

References 28 publications

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“…We suppose that the contribution of NAc dopaminergic receptors in modulation of LH‐induced analgesia may be related to orexin transmission in the VTA. These findings are in line with previous studies, which showed that intra‐NAc administration of dopamine receptor antagonists reduced LH‐induced analgesia in the tail‐flick test (Moradi et al., ,b). This demonstrates that NAc is a common substrate for modulation of phasic and tonic pain.…”

Section: Discussionsupporting

confidence: 93%

“…Previous studies have revealed that intra‐LH injection of carbachol, a cholinergic receptor agonist, reduced nociceptive responses in the phasic, tonic and neuropathic pain models (Holden et al., ; Moradi et al., ,b; Ezzatpanah et al., ). Carbachol increases the firing rate of orexin neurons (Ohno et al., ).…”

Section: Discussionmentioning

confidence: 97%

“…Electrical stimulation of the lateral hypothalamus (LH) induces analgesia in the formalin test (Lopez et al., ). In addition, carbachol, a cholinergic receptor agonist, increases the firing rate of LH neurons including SP and orexin neurons and attenuates nociceptive responses in the acute and formalin‐induced pain models (Holden and Pizzi, ; Ohno et al., ; Moradi et al., ,b; Ezzatpanah et al., , ). Neuroanatomical evidences have shown that LH has neuronal connections with dopamine neurons in the VTA and NAc neurons (Peyron et al., ).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the VTA dopamine neurons send their projections to the cortical and limbic forebrain regions like the NAc (Fadel and Deutch, ). In our recent studies, we showed that D1‐ and D2‐like dopamine receptors into the VTA and NAc are involved in modulation of LH‐induced analgesia in the tail‐flick test – as a model of acute pain (Moradi et al., ,b). In this respect, it was demonstrated that intra‐VTA or ‐NAc administration of D1‐ and D2‐like dopamine receptor antagonists reduced antinociception induced by intra‐LH injection of carbachol.…”

Section: Introductionmentioning

confidence: 99%

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Nucleus accumbens dopamine receptors mediate hypothalamus‐induced antinociception in the rat formalin test

Siahposht-Khachaki

Pourreza

Ezzatpanah

et al. 2017

European Journal of Pain

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Background: Lateral hypothalamus (LH) involves in modulation of tonic pain. Regarding the direct and indirect neural connections between the LH and nucleus accumbens (NAc), we aimed to examine the pain modulatory role of NAc dopamine receptors in modulation of LH-induced analgesia in the formalin test. Methods: Vehicle-control groups received saline or DMSO into the NAc and saline into the LH. Carbachol-control groups received carbachol (250 nmol/L) into the LH, 5 min after saline or DMSO injection into the NAc. In treatment groups, intra-NAc administration of SCH-23390 or sulpiride (D1-and D2-like dopamine receptor antagonists, respectively) was performed 5 min before carbachol injection. Formalin test was done in all rats 5 min after the second injection. Results: The blockade of NAc dopamine receptors reduced carbacholinduced antinociception during both phases of formalin test and reduction in LH-induced analgesia during the late phase was more than that during the early phase. Furthermore, contribution of D2-like dopamine receptors to mediation of anti-hyperalgesic effect of carbachol was greater than that of D1-like dopamine receptors during the late phase. Conclusions: The findings suggest that LH-VTA-NAc circuit is contributed to the modulation of formalin-induced pain. These findings demonstrate that transmission at D1-and D2-like dopamine receptors mediates the LH-induced analgesia. Significance: Blockade of accumbal dopamine receptors attenuated analgesia induced by carbachol injection into the lateral hypothalamus during both phases of formalin test. Effect of blockade of D1-and D2-like dopamine receptors on reduction in antinociception was more during the late phase. Contribution of D2-like dopamine receptors to mediation of antinociception during the late phase was greater than the early phase.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nucleus accumbens dopamine receptors mediate hypothalamus‐induced antinociception in the rat formalin test

Siahposht-Khachaki

Pourreza

Ezzatpanah

et al. 2017

European Journal of Pain

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“…Furthermore, a few reports have focused on the roles of different DA receptors in pain modulation. Pretreatment of VTA with both sulpiride [64] and SCH-23390 [65] could inhibit antinociception induced by intralateral hypothalamus (LH) microinjection of carbachol, obtained by the tail-flick test. The precise function of VTA DA neurons in the pain process is still unclear.…”

Section: Ventral Tegmental Area (Vta)mentioning

confidence: 99%

The Distinct Functions of Dopaminergic Receptors on Pain Modulation: A Narrative Review

et al. 2021

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Chronic pain is considered an economic burden on society as it often results in disability, job loss, and early retirement. Opioids are the most common analgesics prescribed for the management of moderate to severe pain. However, chronic exposure to these drugs can result in opioid tolerance and opioid-induced hyperalgesia. On pain modulation strategies, exploiting the multitarget drugs with the ability of the superadditive or synergistic interactions attracts more attention. In the present report, we have reviewed the analgesic effects of different dopamine receptors, particularly D1 and D2 receptors, in different regions of the central nervous system, including the spinal cord, striatum, nucleus accumbens (NAc), and periaqueductal gray (PAG). According to the evidence, these regions are not only involved in pain modulation but also express a high density of DA receptors. The findings can be categorized as follows: (1) D2-like receptors may exert a higher analgesic potency, but D1-like receptors act in different manners across several mechanisms in the mentioned regions; (2) in the spinal cord and striatum, antinociception of DA is mainly mediated by D2-like receptors, while in the NAc and PAG, both D1- and D2-like receptors are involved as analgesic targets; and (3) D2-like receptor agonists can act as adjuvants of μ-opioid receptor agonists to potentiate analgesic effects and provide a better approach to pain relief.

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Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat

Sibi

Yang

et al. 2016

Exp Brain Res

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Deep brain stimulation has been found to be effective in relieving intractable pain. The ventral tegmental area (VTA) plays a role not only in the reward process, but also in the modulation of nociception. Lesions of VTA result in increased pain thresholds and exacerbate pain in several pain models. It is hypothesized that direct activation of VTA will reduce pain experience. In this study, we investigated the effect of direct electrical stimulation of the VTA on mechanical, thermal and carrageenan-induced chemical nociceptive thresholds in Sprague-Dawley rats using our custom-designed wireless stimulator. We found that: (1) VTA stimulation itself did not show any change in mechanical or thermal threshold; and (2) the decreased mechanical and thermal thresholds induced by carrageenan injection in the hind paw contralateral to the stimulation site were significantly reversed by VTA stimulation. To further explore the underlying mechanism of VTA stimulation-induced analgesia, spinal cord dorsal horn neuronal responses to graded mechanical stimuli were recorded. VTA stimulation significantly inhibited dorsal horn neuronal activity in response to pressure and pinch from the paw, but not brush. This indicated that VTA stimulation may have exerted its analgesic effect via descending modulatory pain pathways, possibly through its connections with brain stem structures and cerebral cortex areas.

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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

Cited by 14 publications

References 28 publications

Nucleus accumbens dopamine receptors mediate hypothalamus‐induced antinociception in the rat formalin test

Nucleus accumbens dopamine receptors mediate hypothalamus‐induced antinociception in the rat formalin test

The Distinct Functions of Dopaminergic Receptors on Pain Modulation: A Narrative Review

Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat

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