scholarly journals Anxiolytic effect of GABAergic neurons in the anterior cingulate cortex in a rat model of chronic inflammatory pain

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fang-bing Shao ◽  
Jun-fan Fang ◽  
Si-si Wang ◽  
Meng-ting Qiu ◽  
Dan-ning Xi ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Anterior Cingulate Cortex ◽  
Rat Model ◽  
Inflammatory Pain ◽  
Pyramidal Neurons ◽  
Cingulate Cortex ◽  
Gabaergic Neurons ◽  
Gabaergic System ◽  
Anterior Cingulate ◽  
Chronic Inflammatory Pain

AbstractChronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABAAR agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABAAR antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety.

scholarly journals Depressive-like States Heighten the Aversion to Painful Stimuli in a Rat Model of Comorbid Chronic Pain and Depression

2012 ◽  
Vol 117 (3) ◽  
pp. 613-625 ◽  
Author(s):  
Lidia Bravo ◽  
Juan Antonio Mico ◽  
Raquel Rey-Brea ◽  
Beatriz Pérez-Nievas ◽  
Juan Carlos Leza ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Anterior Cingulate Cortex ◽  
Rat Model ◽  
Chronic Mild Stress ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Mild Stress ◽  
Sham Control ◽  
Neuronal Density ◽  
Extracellular Signal

Background Chronic pain and depression are two complex states with sensory/somatic and emotional components, and they may mutually exacerbate one another in conditions of comorbidity, leading to a poorer prognosis. Methods The authors have evaluated the sensory and emotional components in a rat model combining chronic constriction injury (CCI, a model of chronic neuropathic pain) with unpredictable chronic mild stress (CMS, an experimental model of depression). In addition, the phosphorylation/activation of the extracellular signal-regulated kinases 1 and 2 and neuronal density was also evaluated in the anterior cingulate cortex. Four groups were tested: sham-control, sham-CMS, CCI-control, and CCI-CMS. Results CMS selectively heightens aversion to painful experiences in animals subjected to CCI, as measured in the place escape/avoidance test at 20, 25, and 30 min (CCI-CMS (mean±SEM): 75.68±3.32, 66.75±4.70, 77.54±3.60 vs. CCI-control: 44.66±6.07, 43.17±6.92, 52.83±5.92, respectively), in conjunction with an increase in the accumulation of phosphorylation/activation of the extracellular signal-regulated kinases (CCI-CMS: 4.17±0.52 vs. sham-control: 0.96±0.05) and a decrease in neuronal density in the anterior cingulate cortex. In contrast, chronic pain did not exacerbate the characteristic profile of depression (anhedonia and behavioral despair) in rats subjected to CMS. Furthermore, depression enhances the perception of some specific modalities of sensorial pain such as cold allodynia but has no influence on mechanical threshold. Conclusions These findings support the theory that depression leads to emotional dysfunction in the interpretation of pain in patients suffering chronic pain. In addition, combined animal models of pain-depression may provide a valuable tool to study the comorbidity of pain and depression.

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

2021 ◽  
Vol 15 ◽  
Author(s):  
Fangbing Shao ◽  
Junfan Fang ◽  
Mengting Qiu ◽  
Sisi Wang ◽  
Danning Xi ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Inflammatory Pain ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Aminobutyric Acid ◽  
Anxiety And Depression ◽  
Pain Sensation ◽  
Pain Model ◽  
Chronic Inflammatory Pain ◽  
Underlying Mechanisms

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.

scholarly journals Electroacupuncture Alleviates Chronic Pain-Induced Anxiety Disorders by Regulating the rACC-Thalamus Circuitry

2021 ◽  
Vol 14 ◽  
Author(s):  
Zui Shen ◽  
Haiyan Zhang ◽  
Zemin Wu ◽  
Qiaoying He ◽  
Jinggen Liu ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Anxiety Disorders ◽  
Anterior Cingulate Cortex ◽  
Rat Model ◽  
Cingulate Cortex ◽  
Mechanistic Explanation ◽  
Anterior Cingulate ◽  
Intraplantar Injection ◽  
Rostral Anterior Cingulate Cortex ◽  
Underlying Mechanisms

Anxiety is a common comorbidity associated with chronic pain, which results in chronic pain complexification and difficulty in treatment. Electroacupuncture (EA) is commonly used to treat chronic pain and anxiety. However, the underlying mechanisms of the EA effect are largely unknown. Here, we showed that a circuitry underlying chronic pain induces anxiety disorders, and EA can treat them by regulating such circuitry. Using chemogenetic methods, we found that chemogenetic activation of the rostral anterior cingulate cortex (rACC) glutamatergic output to the thalamus induced anxiety disorders in control rats. Then, chemogenetic inhibition of the rACC-thalamus circuitry reduced anxiety-like behavior produced by intraplantar injection of the complete Freund’s adjuvant (CFA). In this study, we examined the effects of EA on a rat model of CFA-mediated anxiety-like behaviors and the related mechanisms. We found that chemogenetic activation of the rACC-thalamus circuitry effectively blocked the effects of EA on chronic pain-induced anxiety-like behaviors in CFA rats. These results demonstrate an underlying rACC-thalamus glutamatergic circuitry that regulates CFA-mediated anxiety-like behaviors. This study also provides a potential mechanistic explanation for EA treatment of anxiety caused by chronic pain.

scholarly journals Chronic inflammatory pain induced GABAergic synaptic plasticity in the adult mouse anterior cingulate cortex

2018 ◽  
Vol 14 ◽  
pp. 174480691878347 ◽  
Author(s):  
Kohei Koga ◽  
Shuji Shimoyama ◽  
Akihiro Yamada ◽  
Tomonori Furukawa ◽  
Yoshikazu Nikaido ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Anterior Cingulate Cortex ◽  
Inflammatory Pain ◽  
Adult Mouse ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Chronic Inflammatory Pain
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