Glutamate/GABA balance in ACC modulates the nociceptive responses of vocalization: An expression of affective-motivational component of pain in guinea pigs

Zugaib, João; Coutinho, Mário Sérgio Soares de Azeredo; Ferreira, Mateus Dalbem; Menescal-de-Oliveira, Leda

doi:10.1016/j.physbeh.2013.12.004

Cited by 19 publications

(11 citation statements)

References 47 publications

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“…There is no doubt that all of this evidence suggests that hyperexcitability of the ACC is involved in pain and pain-related negative emotions. Activity of ACC neurons is necessary and sufficient for the coding and processing of pain and the accompanying emotional pain, and the balance between neural excitation and inhibition is necessary for the normal function of the ACC (Gong et al, 2010;Zugaib et al, 2014). In chronic pain clinical practice and basic research, changes in neurotransmitters in the central system have been found, which was caused by the dysregulation of GABAergic, glutamatergic, dopaminergic and opioidergic mechanisms (Mhalla et al, 2010;Bannister and Dickenson, 2020;Yang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex

et al. 2021

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Chronic inflammatory pain is a common clinical disease that tends to be associated with negative emotions such as anxiety and depression. The anterior cingulate cortex (ACC) is involved in pain and pain-related anxiety, and γ-aminobutyric acid (GABA)-ergic interneurons play an important role in chronic pain and anxiety. Electroacupuncture (EA) has good analgesic and antianxiety effect, but the underlying mechanisms have not yet been fully elucidated. In this study, we established a chronic inflammatory pain model and observed that this model induced anxiety-like behaviors and decreased the numbers of parvalbumin (PV) and somatostatin (SOM) positive cells. Activation of PV but not SOM interneurons by chemogenetic techniques alleviated anxiety-like behaviors and pain sensation. EA treatment improved pain sensation, anxiety-like behaviors and increased the number of PV- positive cells in the ACC, but did not affect on the number of SOM-positive cells in the ACC. Moreover, specific inhibition of PV interneurons by chemogenetic methods reversed the analgesic and antianxiety effects of EA. These results suggest that EA ameliorates chronic inflammatory pain and pain-related anxiety by upregulating PV but not SOM interneurons in the ACC.

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Section: Discussionmentioning

confidence: 99%

Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex

et al. 2021

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“…Even though we targeted neurons specifically, the Cdh1-expressing lentiviral vector mentioned above was non-selective with no specific promoters to target certain populations of neurons, such as excitatory or inhibitory neurons. Recent studies have reported links between Glutamate/GABA balance in ACC and nociceptive responses, with the overarching idea that GABAergic disinhibition may facilitate glutamate-mediated excitatory transmission in the ACC [ 34 , 35 ]. Not withstanding this limitation, we have found that Cdh1-expressing recombinant lentivirus in SNI rat alleviates the mechanical allodynia and normalised SNI-induced redistribution of AMPA receptor GluR1 subunit and the synaptic ultrastructure in ACC.…”

Section: Discussionmentioning

confidence: 99%

Alleviating Neuropathic Pain Mechanical Allodynia by Increasing Cdh1 in the Anterior Cingulate Cortex

Tan

Yao

et al. 2015

Mol Pain

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BackgroundPlastic changes in the anterior cingulate cortex (ACC) are critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Cdh1, a co-activator subunit of anaphase-promoting complex/cyclosome (APC/C) regulates synaptic differentiation and transmission. Based on this, we hypothesised that the APC/C–Cdh1 played an important role in long-term plastic changes induced by neuropathic pain in ACC.ResultsWe employed spared nerve injury (SNI) model in rat and found Cdh1 protein level in the ACC was down-regulated 3, 7 and 14 days after SNI surgery. We detected increase in c-Fos expression, numerical increase of organelles, swollen myelinated fibre and axon collapse of neuronal cells in the ACC of SNI rat. Additionally, AMPA receptor GluR1 subunit protein level was up-regulated on the membrane through a pathway that involves EphA4 mediated by APC/C–Cdh1, 3 and 7 days after SNI surgery. To confirm the effect of Cdh1 in neuropathic pain, Cdh1-expressing lentivirus was injected into the ACC of SNI rat. Intra-ACC treatment with Cdh1-expressing lentivirus vectors elevated Cdh1 levels, erased synaptic strengthening, as well as alleviating established mechanical allodynia in SNI rats. We also found Cdh1-expressing lentivirus normalised SNI-induced redistribution of AMPA receptor GluR1 subunit in ACC by regulating AMPA receptor trafficking.ConclusionsThese results provide evidence that Cdh1 in ACC synapses may offer a novel therapeutic strategy for treating chronic neuropathic pain.

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“…Despite this there were suggestions that particular limbic structures had a distinct role in the production of calls such as the isolation whistle. Thus the ACC was thought to be involved in gating the production of most innate calls [ 18 ] but particularly the pup isolation whistle [ 45 ]. The basolateral amygdaloid nucleus was also thought to be involved in the production of isolation whistles in guinea pig pups through the release of substance P into the amygdala caused by the increased stress [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Communication calls produced by electrical stimulation of four structures in the guinea pig brain

Green¹,

Shackleton²,

Grimsley³

et al. 2018

PLoS ONE

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One of the main central processes affecting the cortical representation of conspecific vocalizations is the collateral output from the extended motor system for call generation. Before starting to study this interaction we sought to compare the characteristics of calls produced by stimulating four different parts of the brain in guinea pigs (Cavia porcellus). By using anaesthetised animals we were able to reposition electrodes without distressing the animals. Trains of 100 electrical pulses were used to stimulate the midbrain periaqueductal grey (PAG), hypothalamus, amygdala, and anterior cingulate cortex (ACC). Each structure produced a similar range of calls, but in significantly different proportions. Two of the spontaneous calls (chirrup and purr) were never produced by electrical stimulation and although we identified versions of chutter, durr and tooth chatter, they differed significantly from our natural call templates. However, we were routinely able to elicit seven other identifiable calls. All seven calls were produced both during the 1.6 s period of stimulation and subsequently in a period which could last for more than a minute. A single stimulation site could produce four or five different calls, but the amygdala was much less likely to produce a scream, whistle or rising whistle than any of the other structures. These three high-frequency calls were more likely to be produced by females than males. There were also differences in the timing of the call production with the amygdala primarily producing calls during the electrical stimulation and the hypothalamus mainly producing calls after the electrical stimulation. For all four structures a significantly higher stimulation current was required in males than females. We conclude that all four structures can be stimulated to produce fictive vocalizations that should be useful in studying the relationship between the vocal motor system and cortical sensory representation.

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Glutamate/GABA balance in ACC modulates the nociceptive responses of vocalization: An expression of affective-motivational component of pain in guinea pigs

Cited by 19 publications

References 47 publications

Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex

Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex

Alleviating Neuropathic Pain Mechanical Allodynia by Increasing Cdh1 in the Anterior Cingulate Cortex

Communication calls produced by electrical stimulation of four structures in the guinea pig brain

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