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

Siahposht-Khachaki, Ali; Pourreza, Pooya; Ezzatpanah, Somayeh; Haghparast, Abbas

doi:10.1002/ejp.1029

Cited by 19 publications

(8 citation statements)

References 27 publications

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“…However, the D1selective agonist SKF-38393 had no significant effect on the nociceptive behavior induced by formalin [70]. Even so, a number of reports have demonstrated that blocking both D1-and D2-like receptors of the NAc attenuated analgesia induced by forced swim stress [72] and carbachol injection into the LH [73] in the formalin test, particularly in the late phase. And intra-accumbal administration of SCH-23390 and sulpiride dose-dependently prevented intra-VTA orexin-induced antinociception measured by the tail-flick test [74].…”

Section: Nucleus Accumbens (Nac)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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Section: Nucleus Accumbens (Nac)mentioning

confidence: 99%

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

et al. 2021

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“…Effect of blockade of D1-and D2-like dopamine receptors on reduction in anti-nociception was more during the late phase. The contribution of D2-like dopamine receptors to mediation of antinociception during the late phase was greater than the early phase [17] . In this study, pretreatment of mice with sulpiride (D2 receptor antagonist) did not affect HeCPinduced anti-nociception.…”

Section: Discussionmentioning

confidence: 76%

Anti-Nociceptive and Anti-Inflammatory Activities of the Hydroethanolic Extract of the Leaf of Clerodendrum polycephalum (Lamiaceae)

Oo¹,

Io²,

Aa³

et al. 2018

IJLSSR

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Background-The mainstay of the treatment of pain and inflammation are opioids, steroids, and non-steroidal anti-inflammatory drugs. Though, they are effective and readily available with negative and unpleasant effects, more importantly, hepatotoxicity and nephrotoxicity. Thus, the need for safer and effective therapy in the management of pain and inflammation. Objective-The work sought to investigate the anti-nociceptive and anti-inflammatory activities of the hydro-ethanolic leaf extract of Clerodendrum polycephalum (HeCP) in animals. Methods-HeCP (100, 200 or 400 mg/kg, p.o.) given to mice, 1 h before administer of acetic acid (0.6% v/v, i.p.), formalin (1%v/v, intraplantar) or capsaicin (1% w/v, intraplantar) for nociceptive behavior in mice while carrageenan (1% w/v in saline, intraplantar) or cotton pellet (20 mg implanted into both groin) to induce acute or chronic inflammation in rats. Results-HeCP (100 -400 mg/kg, p.o.) reduced mean writhes number, duration of paw licking or biting in the acetic acid, formalin and capsaicin models, respectively, in mice. However, the initial treatment of mice with L-NNA (neuronal nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), or glibenclamide (ATP-sensitive K + channel blocker) prevented HeCP induced anti-nociception in mice. In contrast, the initial treatment of mice with, sulpiride (dopamine D 2 -receptor antagonist) failed to reverse HeCP-induced antinociception. In the aspect of anti-inflammatory activity, HeCP caused significantly but not dose-dependent inhibition of edema development in carrageenan-induced inflammation and cotton pellet-induced granuloma formation in rats. Conclusion-Findings from this work indicates that the hydroethanolic leaf extract of Clerodendrum polycephalum has anti-nociceptive and anti-inflammatory possibly due to its polyphenolic constituents.

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“…Each level on this scale can be weighted to optimize the test (Abbott et al, 1995; Coderre et al, 1993). In addition, recent studies conducted in this laboratory have used the same method (Ezzatpanah et al., 2016; Siahposht‐Khachaki et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

“…As mentioned above, pain behaviours were scored as follows: 0, the posture and position of the injected paw was indistinguishable from the contralateral paw; 1, little or no weight placed on the injected paw; 2, the injected paw was elevated and had no contact with any surface and 3, the injected paw was licked or bitten. Nociceptive behaviour test commenced immediately after formalin injection (time 0), and the time‐course responses of pain behaviour were recorded in 5‐min blocks for 60 min test period (Ezzatpanah et al., 2016; Siahposht‐Khachaki et al, 2017). The behavioural responses during the early (1–7 min), interphase (8–14 min) and the late phases (15–60 min) were separately evaluated in each group.…”

Section: Methodsmentioning

confidence: 99%

“…Both rewarding and aversive stimuli, such as stressors, are known to rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA) and nucleus accumbens (NAc) (Holly & Miczek, 2016). The VTA‐NAc circuit participates in pain modulation through different neuromodulators such as glutamate, γ‐aminobutyric acid (GABA), serotonin, dopamine and orexin (Hikosaka et al., 2008; Siahposht‐Khachaki et al., 2017). The nucleus accumbens, as an important component of the mesolimbic dopaminergic reward system, plays a role in pain modulation via two types of dopamine receptors: D1‐like (which includes D1 and D5) and D2‐like (include D2, D3 and D4) receptors (Missale et al., 1998).…”

Section: Introductionmentioning

confidence: 99%

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Intra‐accumbal dopaminergic system modulates the restraint stress‐induced antinociceptive behaviours in persistent inflammatory pain

Faramarzi

Charmchi

Salehi

et al. 2021

European Journal of Pain

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Background: Stress activates several neural pathways that inhibit pain sensation. Nucleus accumbens (NAc), as an important component of the mesolimbic dopaminergic system, has a major role in pain modulation and is differentially affected by stress. Based on the nature of stressors, the direction of this effect is controversial. We previously showed that forced swim stress-induced analgesia through activation of NAc dopamine receptors. In this study, we aimed to examine the role of dopamine receptors within the NAc in restraint stress (RS)-induced analgesia. Methods: Male Wistar rats weighing 230-250 g were unilaterally implanted with a cannula into the NAc. D1-like dopamine receptor antagonist, SCH-23390 (0.25, 1 and 4 µg/0.5 µL saline), or D2-like dopamine receptor antagonist, Sulpiride (0.25, 1 and 4µg/0.5µl DMSO), were microinjected into NAc in two separate super groups 5 min prior to exposure to RS. Their control groups just received intra-accumbal saline or DMSO (0.5 µl) respectively. The formalin test was performed after animals were subjected to RS using Plexiglas tubes. Results: The results demonstrated that RS produces analgesia in both phases of the formalin test. Intra-NAc injection of SCH-23390 equally reduced RS-induced analgesia in both early and late phases of the formalin test, while Sulpiride reduced RSinduced analgesia just at the late phase. Conclusions: These findings suggest that the dopaminergic system might act as a potential endogenous pain control system in stress conditions. However, the lack of evaluation of the role of the dopaminergic system in RS-induced antinociception in acute pain conditions is considered as a limitation for this study. In addition, a comprehensive evaluation of this endogenous pain control system in animal and clinical studies will guide future efforts for developing more effective medication. Significance: Restraint stress (RS) induces the antinociceptive behaviors in both phases of formalin test. Blockade of intra-accumbal dopamine receptors impresses the antinociception induced by RS. Blockade of D1-like dopamine receptor equally reduced RS-induced analgesia in both early and late phases of the formalin test.

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

Cited by 19 publications

References 27 publications

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

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

Anti-Nociceptive and Anti-Inflammatory Activities of the Hydroethanolic Extract of the Leaf of Clerodendrum polycephalum (Lamiaceae)

Intra‐accumbal dopaminergic system modulates the restraint stress‐induced antinociceptive behaviours in persistent inflammatory pain

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