Upregulation of tumor necrosis factor-alpha in the anterior cingulate cortex contributes to neuropathic pain and pain-associated aversion

Yao, Pei-Wen; Wang, Shaokun; Chen, Shao-Xia; Xin, Wenjun; Liu, Xian-Guo; Zang, Ying

doi:10.1016/j.nbd.2019.04.012

Cited by 21 publications

(59 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rACC is a higher center for processing affective emotions (Yao et al, 2019). In the central nervous system, the rACC integrates pain and emotional information from the frontal cortex, thalamus, and amygdala (Zheng et al, 2018;Liu et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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

Shen

Zhang

et al. 2021

Front. Neurosci.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Shen

Zhang

et al. 2021

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The small sample size likely precluded detecting more highly significant differences in thermal and pressure sensitivity. TNF has a plethora of other roles in the central nervous system for regulating neuronal function, synaptic plasticity and neurotransmitter activity related to pain [62,63,64,65] which may also underlie mechanisms associated with the persistence of CPSP and the effects of anti-TNF detected here.…”

Section: Discussionmentioning

confidence: 81%

Phase I/II parallel double-blind randomized controlled clinical trial of perispinal etanercept for chronic stroke: improved mobility and pain alleviation

Ralph

Weissenberger

Bonev

et al. 2020

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

show abstract

“…As described previously [33], animals were anesthetized and perfused through the ascending aorta with 0.9% saline followed by 4% paraformaldehyde in 0.1 M phosphate buffer (PB). Following perfusion brains were removed and post xed for 5 h, then dehydrated in 30% sucrose for 5 days.…”

Section: Immunohistochemistry and Immuno Uorescencementioning

confidence: 99%

“…As described previously [33], mice were deeply anesthetized (1%-2% iso urane) and then mounted in a stereotaxic frame with nonpuncturing ear bars. To selectively express hM4Di (Gi-coupled human M4 muscarinic receptor) or hM3Dq (Gq-coupled human M3 muscarinic receptor) in ACC excitatory pyramidal neurons, the pAOV-CaMK a-hM4D(Gi)-mCherry-3Flag (hM4Di-mCherry) or pAAV-CaMK a-hM3D(Gq)-mCherry (hM3Dq-mCherry) were injected into the contralateral (right) ACC of mice with or without SNI surgery, respectively.…”

Section: Western Blottingmentioning

confidence: 99%

Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury

Yao

Liu

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus results in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain. Methods: The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC pyramidal neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling.Results: Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC pyramidal neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6. Conclusions: The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.

show abstract

Upregulation of tumor necrosis factor-alpha in the anterior cingulate cortex contributes to neuropathic pain and pain-associated aversion

Cited by 21 publications

References 75 publications

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

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

Phase I/II parallel double-blind randomized controlled clinical trial of perispinal etanercept for chronic stroke: improved mobility and pain alleviation

Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury

Contact Info

Product

Resources

About