A D2-like receptor family agonist produces analgesia in mechanonociception but not in thermonociception at the spinal cord level in rats

Almanza, Angélica; Simón-Arceo, Karina; Coffeen, Ulises; Fuentes–García, Ruth; Contreras, Bernardo; Pellicer, Francisco; Mercado, Francisco García Gómez de

doi:10.1016/j.pbb.2015.08.013

Cited by 20 publications

(14 citation statements)

References 34 publications

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“…A recent study by Almanza et al has demonstrated that small doses of a D2-like receptor agonist have an antinociceptive effect in treatment-naive rats 6. The results of their study are not consistent with our findings in terms of the requirement for high doses of quinpirole to exert analgesic effects in the postoperative pain model.…”

Section: Discussioncontrasting

confidence: 99%

“…The results of their study are not consistent with our findings in terms of the requirement for high doses of quinpirole to exert analgesic effects in the postoperative pain model. The exact reasons for this discrepancy are not clear, but Almanza et al suggested the possibility that a D2-like receptor agonist may have a nonspecific action when administered at high doses 6. Further studies are needed to clarify this matter.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been reported that activation of the spinal D1-like receptor exacerbates N -methyl- d -aspartate receptor-induced hyperexcitability5 and the intrathecal (IT) administration of a D2-like receptor agonist has an antinociceptive effect in rats 6. Further, there is some evidence that the neuroplasticity contributing to the development of pathological pain states may be mediated by a D1/D5 mechanism in the spinal cord 7.…”

Section: Introductionmentioning

confidence: 99%

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D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

Ohtani

Masaki

2016

JPR

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BackgroundApproximately half of all patients who undergo surgery develop postoperative pain, the mechanisms of which are not well understood by anesthesiologists. D2-like receptors in the descending dopaminergic pathway play an important role in regulation of pain transmission in the spinal cord. Impairment of inhibitory neurons in the spinal cord is suggested as part of the mechanism for neuropathic pain, which is one component of postoperative pain. The purpose of this study was to investigate whether impairment of D2-like receptors in the descending dopaminergic pathway in the spinal cord is involved in the decreased postoperative nociceptive threshold in rats.MethodsMale Sprague-Dawley rats (250–300 g) were anesthetized with sevoflurane and an intrathecal (IT) catheter was implanted. Six days later, a plantar incision was made. On the following day, saline, a D2-like receptor agonist (quinpirole), or a D2-like receptor antagonist (sulpiride) was administered intrathecally. Thermal and mechanical nociceptive responses were assessed by exposure to infrared radiant heat and the von Frey filament test before and after plantar incision.ResultsPlantar incision decreased both thermal latency and the mechanical nociceptive threshold. IT administration of quinpirole inhibited the nociceptive responses induced by plantar incision, but sulpiride had no effect.ConclusionA D2-like receptor agonist had antinociceptive effects on the hypersensitivity response triggered by a surgical incision, but a D2-like receptor antagonist had no effect on this response. These results suggest that impairment and/or modification of D2-like receptors in the descending dopaminergic pathway in the spinal cord is not involved in the postoperative decrease in nociceptive threshold.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

Ohtani

Masaki

2016

JPR

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“… 44 , 45 Moreover, the antinociceptive effect of mazindol was blocked by a D2-like receptor antagonist, but not by a D1-like receptor antagonist or an opioid receptor antagonist. In line with these findings, different studies have shown that spinal 46 , 47 and supraspinal 48 , 49 administration of D2-like receptor agonists, but not D1-like receptor agonists, 49 resulted in antinociceptive effects in different experimental pain models.…”

Section: Discussionsupporting

confidence: 62%

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

et al. 2017

JPR

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BackgroundThe role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund’s adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined.MethodsAdult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15–day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography.ResultsAcute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic and nonarthritic knee joints.ConclusionResults suggest that mazindol via D2-like receptors has an antinociceptive role in mice with CFA-induced knee arthritis without modifying the bone health negatively.

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“…A central role of dopaminergic transmission in modulating pain perception within supraspinal and spinal regions has been demonstrated [ 30 ]. Striatal or spinal cord level of dopamine D2 receptor stimulation has been shown to exhibit antinociceptive effects in acute pain [ 36 – 38 ] and neuropathic pain [ 39 – 42 ]. These seemingly contradictory results could be explained by the preferential presynaptic D2 autoreceptor activation of some of the D2 receptor antagonists.…”

Section: Discussionmentioning

confidence: 99%

The Antinociceptive Properties of the Corydalis yanhusuo Extract

et al. 2016

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Corydalis yanhusuo. W.T. extracts (YHS) are widely used for the treatment of pain and inflammation. There are a few studies that assessed the effects of YHS in pain assays; however, none of these studies has systematically compared its activities in the different pain animal modes namely: acute, inflammatory and chronic pain. Furthermore, little is known about the mechanism of YHS activity in these assays. The aim of this study was to systematically evaluate the antinociceptive properties of YHS by testing it in four standardized pain assays and to investigate its mechanism. YHS antinociceptive properties were analyzed in the tail flick, the formalin paw licking, the von Frey filament and the hot box assays after spinal nerve ligation, which monitors acute nociceptive, persistent inflammatory and chronic neuropathic pain, respectively. YHS pharmacological profile was determined by screening it against a battery of G-protein coupled receptors and its mechanism of action was studied using knock-out mice. Our study shows that YHS, at a non-sedative dose, increases the tail flick latency in the tail flick assay without resulting in development of tolerance. YHS also decreases paw licking time in the formalin assay. Further, YHS increases paw withdraw threshold and latency in the von Frey filament and the hot box assays, respectively. In vitro, YHS exhibits prominent dopamine receptor antagonistic properties. In dopamine D2 receptor knockout mice, its antinociceptive effects are attenuated in acute and neuropathic pain but not inflammatory pain assays. Our results therefore indicate that YHS effectively attenuates acute, inflammatory and neuropathic pain, without causing tolerance. The effects on acute and neuropathic pain, but not inflammatory pain, are at least partially mediated through dopamine D2 receptor antagonism. Since YHS is a dietary supplement commercially available in the United States, our data suggest that it might be a candidate for alternative pain treatment.

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A D2-like receptor family agonist produces analgesia in mechanonociception but not in thermonociception at the spinal cord level in rats

Cited by 20 publications

References 34 publications

D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

The Antinociceptive Properties of the Corydalis yanhusuo Extract

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A D2-like receptor family agonist produces analgesia in mechanonociception but not in thermonociception at the spinal cord level in rats

Cited by 20 publications

References 34 publications

D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund&rsquo;s adjuvant-induced knee arthritis

The Antinociceptive Properties of the Corydalis yanhusuo Extract

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Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis