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

Shao, Fangbing; Fang, Jiaqi; Qiu, Mengting; Wang, Sisi; Xi, Danning; Shao, Xiaomei; He, Xiaofen; Fang, Jianqiao; Du, Junying

doi:10.3389/fnins.2021.691931

Cited by 22 publications

(15 citation statements)

References 74 publications

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“…The subtypes of GABAergic neurons mainly include parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) [26]. Our previous paper has been observed that only PV interneurons were involved in chronic inflammatory pain related anxiety-like behaviors and pain sensation [27]. We observed the expression of PV positive cells and its coexpression with c-Fos.…”

Section: Reduction Of Inhibitory Presynaptic Transmission In the Acc ...mentioning

confidence: 78%

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

et al. 2021

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Chronic 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.

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Section: Reduction Of Inhibitory Presynaptic Transmission In the Acc ...mentioning

confidence: 78%

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

et al. 2021

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“…As a common analgesic method worldwide, EA affects multiple targets and acts on multiple levels, and EA has been widely used in the clinic and has been shown to achieve good clinical effects [ 40 – 42 ]. Accumulated evidence has found that EA can alleviate the abnormal pain sensation and negative emotions induced by chronic pain in rats [ 26 , 27 , 43 ]. We previously reported the analgesic and antidepressant effects of EA at different frequencies [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…Electroacupuncture (EA) is effective for relieving pain and emotional diseases [ 26 , 27 ]. Moreover, it is widely used in China and all over the world because it is safer, more effective, and has fewer side effects than other treatments.…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture Alleviates Anxiety-Like Behaviors Induced by Chronic Neuropathic Pain via Regulating Different Dopamine Receptors of the Basolateral Amygdala

Chen

Shen

et al. 2022

Mol Neurobiol

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Chronic pain, such as neuropathic pain, causes anxiety and other negative emotions, which aggravates the pain sensation and increases the risk of chronic pain over time. Dopamine receptor D1 (DRD1) and dopamine receptor D2 (DRD2) in the basolateral amygdala (BLA) have been implicated in mediating anxiety-related behaviors, but their potential roles in the BLA in neuropathic pain-induced anxiety have not been examined. Electroacupuncture (EA) is commonly used to treat chronic pain and emotional disorders, but it is still unclear whether EA plays a role in analgesia and anxiety relief through DRD1 and DRD2 in the BLA. Here, we used western blotting to examine the expression of DRD1 and DRD2 and pharmacological regulation combined with behavioral testing to detect anxiety-like behaviors. We observed that injection of the DRD1 antagonist SCH23390 or the DRD2 agonist quinpirole into the BLA contributed to anxiety-like behaviors in naive mice. EA also activated DRD1 or inhibited DRD2 in the BLA to alleviate anxiety-like behaviors. To further demonstrate the role of DRD1 and DRD2 in the BLA in spared nerve injury (SNI) model-induced anxiety-like behaviors, we injected the DRD1 agonist SKF38393 or the DRD2 antagonist sulpiride into the BLA. We found that both activation of DRD1 and inhibition of DRD2 could alleviate SNI-induced anxiety-like behaviors, and EA had a similar effect of alleviating anxiety. Additionally, neither DRD1 nor DRD2 in the BLA affected SNI-induced mechanical allodynia, but EA did. Overall, our work provides new insights into the mechanisms of neuropathic pain-induced anxiety and a possible explanation for the effect of EA treatment on anxiety caused by chronic pain.

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“…Recent studies have found that SNI induces PV loss and AIS length reduction in the infralimbic cortex [ 62 ]; however, whether SNI causes such structural plasticity in the ACC has remained unclear. Pharmacological or chemogenetic activation of PV-INs, but not SOM-INs, in the ACC was revealed to alleviate mechanical allodynia and anxiety-like behavior in rats with chronic inflammatory pain [ 63 , 64 , 65 ]. PV-IR neurons in the human ACC comprise dendritic and axonal processes, and there are two dense PV-immunolabeled neuropil bands in ACC layers III and V [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

NLRP3-Mediated Piezo1 Upregulation in ACC Inhibitory Parvalbumin-Expressing Interneurons Is Involved in Pain Processing after Peripheral Nerve Injury

Duan²,

Yao-hui³

et al. 2022

IJMS

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The anterior cingulate cortex (ACC) is particularly critical for pain information processing. Peripheral nerve injury triggers neuronal hyper-excitability in the ACC and mediates descending facilitation to the spinal dorsal horn. The mechanically gated ion channel Piezo1 is involved in the transmission of pain information in the peripheral nervous system. However, the pain-processing role of Piezo1 in the brain is unknown. In this work, we found that spared (sciatic) nerve injury (SNI) increased Piezo1 protein levels in inhibitory parvalbumin (PV)-expressing interneurons (PV-INs) but not in glutaminergic CaMKⅡ+ neurons, in the bilateral ACC. A reduction in the number of PV-INs but not in the number of CaMKⅡ+ neurons and a significant reduction in inhibitory synaptic terminals was observed in the SNI chronic pain model. Further, observation of morphological changes in the microglia in the ACC showed their activated amoeba-like transformation, with a reduction in process length and an increase in cell body area. Combined with the encapsulation of Piezo1-positive neurons by Iba1+ microglia, the loss of PV-INs after SNI might result from phagocytosis by the microglia. In cellular experiments, administration of recombinant rat TNF-α (rrTNF) to the BV2 cell culture or ACC neuron primary culture elevated the protein levels of Piezo1 and NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3). The administration of the NLRP3 inhibitor MCC950 in these cells blocked the rrTNF-induced expression of caspase-1 and interleukin-1β (key downstream factors of the activated NLRP3 inflammasome) in vitro and reversed the SNI-induced Piezo1 overexpression in the ACC and alleviated SNI-induced allodynia in vivo. These results suggest that NLRP3 may be the key factor in causing Piezo1 upregulation in SNI, promoting an imbalance between ACC excitation and inhibition by inducing the microglial phagocytosis of PV-INs and, thereby, facilitating spinal pain transmission.

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

Cited by 22 publications

References 74 publications

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

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

Electroacupuncture Alleviates Anxiety-Like Behaviors Induced by Chronic Neuropathic Pain via Regulating Different Dopamine Receptors of the Basolateral Amygdala

NLRP3-Mediated Piezo1 Upregulation in ACC Inhibitory Parvalbumin-Expressing Interneurons Is Involved in Pain Processing after Peripheral Nerve Injury

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