Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain‐related working memory deficits in neuropathic pain rats

Cardoso‐Cruz, Helder; Dourado, Margarida; Monteiro, Clara; Galhardo, Vasco

doi:10.1002/ejp.1186

Cited by 16 publications

(13 citation statements)

References 70 publications

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“…Systemic application of a D2/D3 receptor agonist reversed electrophysiological and memory but not pain-related behavioral deficits in SNI rats. These deficits were exacerbated by systemic administration of a D2 receptor antagonist, which was related to a selective disruption of hippocampal theta oscillations and decrease in intrahippocampal CA1 connectivity [27]. This set of data suggests that cortico-hippocampal interactions are altered in the pain state, and that modulation of dopamine neurotransmission could be involved in these effects.…”

Section: Cortico-hippocampal Interactionsmentioning

confidence: 81%

Cortico-limbic pain mechanisms

Thompson

Neugebauer

2019

Neuroscience Letters

136

113

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Pain has a strong emotional component and is defined by its unpleasantness. Chronic pain represents a complex disorder with anxio-depressive symptoms and cognitive deficits. Underlying mechanisms are still not well understood but an important role for interactions between prefrontal cortical areas and subcortical limbic structures has emerged. Evidence from preclinical studies in the rodent brain suggests that neuroplastic changes in prefrontal (anterior cingulate, prelimbic and infralimbic) cortical and subcortical (amygdala and nucleus accumbens) brain areas and their interactions (corticolimbic circuitry) contribute to the complexity and persistence of pain and may be predetermining factors as has been proposed in recent human neuroimaging studies.

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Section: Cortico-hippocampal Interactionsmentioning

confidence: 81%

Cortico-limbic pain mechanisms

Thompson

Neugebauer

2019

Neuroscience Letters

136

113

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“…Pain affects cognition in humans and rodents since it can divert attention, memory, and decision-making [64]. However, the amount of studies investigating the cognitive deficits associated with the SNI model of neuropathic pain is less than those that have focused on affective disorders [10,33,36,[65][66][67][68]. This discrepancy could reflect the complexity, number, and diversity of paradigms available for measuring cognition.…”

Section: Behavioral Symptoms Associated With the Spared Nerve Injurymentioning

confidence: 99%

“…Working memory deficits were detected in rats mainly using mazes, devices, which exploits the innate leaning (and remembering) of the location associated with safety, food or any other reward in rodents [68]. Working memory impairments were detected at 3-7 days [65] and persisted for a month [34] after SNI surgery. Additionally in rats, attention and reaction time were reduced after 1 month and 3-6 months after the SNI [42,69,70].…”

Section: Behavioral Symptoms Associated With the Spared Nerve Injurymentioning

confidence: 99%

Behavioral, Biochemical and Electrophysiological Changes in Spared Nerve Injury Model of Neuropathic Pain

Guida¹,

Gregorio

Palazzo³

et al. 2020

IJMS

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Neuropathic pain is a pathological condition induced by a lesion or disease affecting the somatosensory system, with symptoms like allodynia and hyperalgesia. It has a multifaceted pathogenesis as it implicates several molecular signaling pathways involving peripheral and central nervous systems. Affective and cognitive dysfunctions have been reported as comorbidities of neuropathic pain states, supporting the notion that pain and mood disorders share some common pathogenetic mechanisms. The understanding of these pathophysiological mechanisms requires the development of animal models mimicking, as far as possible, clinical neuropathic pain symptoms. Among them, the Spared Nerve Injury (SNI) model has been largely characterized in terms of behavioral and functional alterations. This model is associated with changes in neuronal firing activity at spinal and supraspinal levels, and induces late neuropsychiatric disorders (such as anxious-like and depressive-like behaviors, and cognitive impairments) comparable to an advanced phase of neuropathy. The goal of this review is to summarize current findings in preclinical research, employing the SNI model as a tool for identifying pathophysiological mechanisms of neuropathic pain and testing pharmacological agent.

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“…It has been shown that dopamine signalling from the VTA to the NAc is markedly reduced during chronic pain (Taylor et al, 2014), which may be linked not only with comorbidities of pain but also with dysregulation of the local NAcc activation. In this regarding, we have previously reported a significant pain-related disruption of the corticolimbic connectivity during the performance of spatial WM tasks (Cardoso-Cruz, Lima, & Galhardo, 2013a;Cardoso-Cruz, Sousa, et al, 2013b;Monteiro et al, 2016), which occurred associated to an impairment of the dopaminergic signalling (Cardoso-Cruz et al, 2014;Cardoso-Cruz et al, 2018). Another important finding of this study was the fact that the peripheral nerve lesion induced a clear enhancement of spontaneous prefrontal-striatal connectivity, which is mainly mediated by theta-band activity on the ascending pathway (from NAcc to PL-mPFC; Figure 9e) and independent from the motor activity.…”

Section: Discussionmentioning

confidence: 90%

Altered prefrontal‐striatal theta‐band oscillatory dynamics underlie working memory deficits in neuropathic pain rats

Cardoso‐Cruz

Laranjeira

Monteiro

et al. 2022

European Journal of Pain

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Background Prelimbic medial prefrontal cortex (PL‐mPFC) and nucleus accumbens core region (NAcc) play an important role in supporting several executive cognitive mechanisms, such as spatial working memory (WM). Recently, this circuit has been also associated with both sensory and affective components of pain. However, it is still unclear whether this circuit is endogenously engaged in neuropathic pain‐related cognitive dysfunctions. Methods To answer this question, we induced the expression of halorhodopsin in local PL‐mPFC neurons projecting to NAcc, and then selectively inhibited the terminals of these neurons in the NAcc while recording neural activity during the performance of a delayed non‐match to sample (DNMS) spatial WM task. Within‐subject behavioural performance and PL‐mPFC to NAcc circuit neural activity was assessed after the onset of a persistent rodent neuropathic pain model—spared nerve injury (SNI). Results Our results revealed that the induction of the neuropathy reduced WM performance, and altered the interplay between PL‐mPFC and NAcc neurons namely in increasing the functional connectivity from NAcc to PL‐mPFC, particularly in the theta‐band spontaneous oscillations; in addition, these behavioural and functional perturbations were partially reversed by selective optogenetic inhibition of PL‐mPFC neuron terminals into the NAcc during the DNMS task delay‐period, without significant antinociceptive effects. Conclusions Altogether, these results strongly suggest that the PL‐mPFC excitatory output into the NAcc plays an important role in the deregulation of WM under pain conditions. Significance Selective optogenetic inhibition of prefrontal‐striatal microcircuit reverses pain‐related working memory deficits but has no significant impact on pain responses. Neuropathic pain underlies an increase of functional connectivity between the nucleus accumbens core area and the prelimbic medial prefrontal cortex mediated by theta‐band activity.

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Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain‐related working memory deficits in neuropathic pain rats

Cited by 16 publications

References 70 publications

Cortico-limbic pain mechanisms

Cortico-limbic pain mechanisms

Behavioral, Biochemical and Electrophysiological Changes in Spared Nerve Injury Model of Neuropathic Pain

Altered prefrontal‐striatal theta‐band oscillatory dynamics underlie working memory deficits in neuropathic pain rats

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