The Increased In Vivo Firing of Pyramidal Cells But not Interneurons in the Anterior Cingulate Cortex After Neuropathic Pain

2021 ◽  
Author(s):  
Da-Yu Zhu ◽  
Ting-Ting Cao ◽  
Hong-Wei Fan ◽  
Ming-Zhe Zhang ◽  
Hao-Kai Duan ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Firing Rate ◽  
Anterior Cingulate Cortex ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
High Frequency Stimulation ◽  
Nociceptive Information

Abstract Chronic pain damages the balance between excitation and inhibition in the sensory cortex. It has been confirmed that the activity of cortical glutamatergic pyramidal cells increases after chronic pain. However, whether the activity of inhibitory interneurons synchronized changed remains obscure, especially in in vivo conditions. In the present study, we checked the firing rate of pyramidal cells and interneurons in the anterior cingulate cortex, a main cortical area for the regulation of nociceptive information in mice with spared nerve injury by using in vivo multi-channel recording system. We found that the firing rate of pyramidal cells but not interneurons increased in the ACC, which is further confirmed by the increased FOS expression in pyramidal cells but not interneurons, in mice with neuropathic pain. Selectively high frequency stimulation of the ACC nociceptive afferent fibers only potentiated the activity of pyramidal cells either. Our results thus suggest that the increased activity of pyramidal cells contributes to the damaged E/I balance in the ACC and is important for the pain hypersensitivity in mice with neuropathic pain.

scholarly journals Increased burst coding in deep layers of the ventral anterior cingulate cortex during neuropathic pain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fernando Kasanetz ◽  
Thomas Nevian
Keyword(s):  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Neuronal Excitability ◽  
Treatment Strategies ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Electrophysiological Recordings ◽  
Deep Layers ◽  
Noxious Stimuli

AbstractNeuropathic pain induces changes in neuronal excitability and synaptic connectivity in deep layers of the anterior cingulate cortex (ACC) that play a central role in the sensory, emotional and affective consequences of the disease. However, how this impacts ACC in vivo activity is not completely understood. Using a mouse model, we found that neuropathic pain caused an increase in ACC in vivo activity, as measured by the indirect activity marker c-Fos and juxtacellular electrophysiological recordings. The enhanced firing rate of ACC neurons in lesioned animals was based on a change in the firing pattern towards bursting activity. Despite the proportion of ACC neurons recruited by noxious stimuli was unchanged during neuropathic pain, responses to noxious stimuli were characterized by increased bursting. Thus, this change in coding pattern may have important implications for the processing of nociceptive information in the ACC and could be of great interest to guide the search for new treatment strategies for chronic pain.

scholarly journals GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2655-2669 ◽  
Author(s):  
Dina L Juarez-Salinas ◽  
Joao M Braz ◽  
Alexander Etlin ◽  
Steven Gee ◽  
Vikaas Sohal ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Inhibitory Interneuron ◽  
Anterior Cingulate ◽  
Gaba A ◽  
Ongoing Pain ◽  
Rostral Anterior Cingulate Cortex ◽  
Posterior Anterior

Abstract Dysfunction of inhibitory circuits in the rostral anterior cingulate cortex underlies the affective (aversive), but not the sensory-discriminative features (hypersensitivity) of the pain experience. To restore inhibitory controls, we transplanted inhibitory interneuron progenitor cells into the rostral anterior cingulate cortex in a chemotherapy-induced neuropathic pain model. The transplants integrated, exerted a GABA-A mediated inhibition of host pyramidal cells and blocked gabapentin preference (i.e. relieved ongoing pain) in a conditioned place preference paradigm. Surprisingly, pain aversiveness persisted when the transplants populated both the rostral and posterior anterior cingulate cortex. We conclude that selective and long lasting inhibition of the rostral anterior cingulate cortex, in the mouse, has a profound pain relieving effect against nerve injury-induced neuropathic pain. However, the interplay between the rostral and posterior anterior cingulate cortices must be considered when examining circuits that influence ongoing pain and pain aversiveness.

scholarly journals Transcranial Ultrasound Stimulation of the Anterior Cingulate Cortex Reduces Neuropathic Pain in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xiangjun Feng ◽  
Lili Niu ◽  
Meng Long ◽  
Kaixuan Luo ◽  
Xiaowei Huang ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Intervention Group ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Control Group ◽  
Mechanical Threshold ◽  
Stimulation Of

Focused ultrasound (FUS) is a potential tool for treating chronic pain by modulating the central nervous system. Herein, we aimed to determine whether transcranial FUS stimulation of the anterior cingulate cortex (ACC) effectively improved chronic pain in the chronic compress injury mice model at different stages of neuropathic pain. The mechanical threshold of pain was recorded in the nociceptive tests. We found FUS stimulation elevated the mechanical threshold of pain in both short-term ( p < 0.01 ) and long-term ( p < 0.05 ) experiments. Furthermore, we determined protein expression differences in ACC between the control group, the intervention group, and the Sham group to analyze the underlying mechanism of FUS stimulation in improving neuropathic pain. Additionally, the results showed FUS stimulation led to alterations in differential proteins in long-term experiments, including cellular processes, cellular signaling, and information storage and processing. Our findings indicate FUS may effectively alleviate mechanical neuropathic pain via the ACC’s stimulation, especially in the chronic state.

scholarly journals Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bastiaan van der Veen ◽  
Sampath K. T. Kapanaiah ◽  
Kasyoka Kilonzo ◽  
Peter Steele-Perkins ◽  
Martin M. Jendryka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Anterior Cingulate Cortex ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Pyramidal Neurons ◽  
Treatment Options ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Cell Types ◽  
Anterior Cingulate

AbstractPathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of Gi-signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among Gi-coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest Gi-coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders.

scholarly journals Chronic Pain is Associated With Reduced Sympathetic Nervous System Reactivity During Simple and Complex Walking Tasks: Potential Cerebral Mechanisms

2021 ◽  
Vol 5 ◽  
pp. 247054702110302
Author(s):  
Taylor D. Yeater ◽  
David J. Clark ◽  
Lorraine Hoyos ◽  
Pedro A. Valdes-Hernandez ◽  
Julio A. Peraza ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Anterior Cingulate Cortex ◽  
Gray Matter ◽  
Dual Task ◽  
Brain Region ◽  
Skin Conductance Level ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Autonomic Responses ◽  
The Difference

Background Autonomic dysregulation may lead to blunted sympathetic reactivity in chronic pain states. Autonomic responses are controlled by the central autonomic network (CAN). Little research has examined sympathetic reactivity and associations with brain CAN structures in the presence of chronic pain; thus, the present study aims to investigate how chronic pain influences sympathetic reactivity and associations with CAN brain region volumes. Methods Sympathetic reactivity was measured as change in skin conductance level (ΔSCL) between a resting reference period and walking periods for typical and complex walking tasks (obstacle and dual-task). Participants included 31 people with (n = 19) and without (n = 12) chronic musculoskeletal pain. Structural 3 T MRI was used to determine gray matter volume associations with ΔSCL in regions of the CAN (i.e., brainstem, amygdala, insula, and anterior cingulate cortex). Results ΔSCL varied across walking tasks (main effect p = 0.036), with lower ΔSCL in chronic pain participants compared to controls across trials 2 and 3 under the obstacle walking condition. ΔSCL during typical walking was associated with multiple CAN gray matter volumes, including brainstem, bilateral insula, amygdala, and right caudal anterior cingulate cortex (p’s < 0.05). The difference in ΔSCL from typical-to-obstacle walking were associated with volumes of the midbrain segment of the brainstem and anterior segment of the circular sulcus of the insula (p’s < 0.05), with no other significant associations. The difference in ΔSCL from typical-to-dual task walking was associated with the bilateral caudal anterior cingulate cortex, and left rostral cingulate cortex (p’s < 0.05). Conclusions Sympathetic reactivity is blunted during typical and complex walking tasks in persons with chronic pain. Additionally, blunted sympathetic reactivity is associated with CAN brain structure, with direction of association dependent on brain region. These results support the idea that chronic pain may negatively impact typical autonomic responses needed for walking performance via its potential impact on the brain.

scholarly journals Pra-C exerts analgesic effect through inhibiting microglial activation in anterior cingulate cortex in complete Freund’s adjuvant-induced mouse model

2021 ◽  
Vol 17 ◽  
pp. 174480692199093
Author(s):  
Dan-jie Su ◽  
Long-fei Li ◽  
Sai-ying Wang ◽  
Qi Yang ◽  
Yu-jing Wu ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Mouse Model ◽  
Anterior Cingulate Cortex ◽  
Analgesic Effect ◽  
Microglial Activation ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Freund’S Adjuvant ◽  
Complete Freund's Adjuvant ◽  
Freund's Adjuvant

Chronic pain is highly prevalent worldwide and severely affects daily lives of patients and family members. Praeruptorin C (Pra-C) is a main active ingredient derived from Peucedanum praeruptorum Dunn, traditionally used as antibechic, anti-bronchitis and anti-hypertension drug. Here, we evaluated the effects of Pra-C in a chronic inflammatory pain mouse model induced by complete Freund’s adjuvant (CFA) injection. Pra-C (3 mg/kg) treatment for just 3 days after CFA challenge relieved CFA-induced mechanical allodynia and hindpaw edema in mice. In the anterior cingulate cortex (ACC), Pra-C treatment inhibited microglia activation and reduced levels of proinflammatory cytokines, TNF-α and IL-1β, and suppressed upregulation of glutamate receptors caused by CFA injection. In addition, Pra-C attenuated neuronal hyperexcitability in ACC of CFA-injected mice. In vitro studies confirmed the analgesic effect of Pra-C was due to its inhibitory ability on microglial activation. In conclusion, Pra-C administration had a certain effect on relieving chronic pain by inhibiting microglial activation, attenuating proinflammatory cytokine releasing and regulating excitatory synaptic proteins in the ACC of the CFA-injected mice.

Intracortical Circuits in Rat Anterior Cingulate Cortex Are Activated by Nociceptive Inputs Mediated by Medial Thalamus

2006 ◽  
Vol 96 (6) ◽  
pp. 3409-3422 ◽  
Author(s):  
Jenq-Wei Yang ◽  
Hsi-Chien Shih ◽  
Bai-Chuang Shyu
Keyword(s):  
Anterior Cingulate Cortex ◽  
Current Source ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
High Frequency Stimulation ◽  
Evoked Responses ◽  
Synaptic Organization ◽  
Sprague Dawley ◽  
Intracortical Circuits ◽  
Layer V

We investigated the afferents and intracortical synaptic organization of the anterior cingulate cortex (ACC) during noxious electrical stimulation. Extracellular field potentials were recorded simultaneously from 16 electrodes spanning all layers of the ACC in male Sprague–Dawley rats anesthetized by halothane inhalation. Laminar-specific transmembrane currents were calculated with the current source density analysis method. Two major groups of evoked sink currents were identified: an early group (latency = 54.04 ± 2.12 ms; 0.63 ± 0.07 mV/mm2) in layers V–VI and a more intense late group (latency = 80.07 ± 4.85 ms; 2.16 ± 0.22 mV/mm2) in layer II/III and layer V. Multiunit activities were evoked mainly in layer V and deep layer II/III with latencies similar to that of the early and late sink groups. The evoked EPSP latencies of pyramidal neurons in layers II/III and V related closely with the sink currents. The sink currents were inhibited by intracortical injection of CNQX (1 mM, 1 μl), a glutaminergic receptor antagonist, and enhanced by intraperitoneal (5 mg/kg) and intracortical (10 μg/μl, 1 μl) injection of morphine, a μ-opioid receptor agonist. Paired-pulse depression was observed with interpulse intervals of 50 to 1,000 ms. High-frequency stimulation (100 Hz, 11 pulses) enhanced evoked responses in the ACC and evoked medial thalamic (MT) unit activities. MT lesions blocked evoked responses in the ACC. Our results demonstrated that two distinct synaptic circuits in the ACC were activated by noxious stimuli and that the MT is the major thalamic relay that transmits nociceptive information to the ACC.

Role for NMDA receptors in visceral nociceptive transmission in the anterior cingulate cortex of viscerally hypersensitive rats

2008 ◽  
Vol 294 (4) ◽  
pp. G918-G927 ◽  
Author(s):  
Xiaoyin Wu ◽  
Jun Gao ◽  
Jin Yan ◽  
Jing Fan ◽  
Chung Owyang ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Neuronal Firing ◽  
Anterior Cingulate ◽  
High Dose ◽  
Glutamatergic Transmission ◽  
Reverse Microdialysis

We have identified colorectal distension (CRD)-responsive neurons in the anterior cingulate cortex (ACC) and demonstrated that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization. In the present study, we confirmed that rostral ACC neurons of sensitized rats [induced by chicken egg albumin (EA)] exhibit enhanced spike responses to CRD. Simultaneous in vivo recording and reverse microdialysis of single ACC neurons showed that a low dose of glutamate (50 μM) did not change basal ACC neuronal firing in normal rats but increased ACC neuronal firing in EA rats from 18 ± 2 to 32 ± 3.8 impulses/10 s. A high dose of glutamate (500 μM) produced 1.95-fold and a 4.27-fold increases of ACC neuronal firing in sham-treated rats and in EA rats, respectively, suggesting enhanced glutamatergic transmission in the ACC neurons of EA rats. Reverse microdialysis of the 3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainite receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 μM) reduced basal and abolished CRD-induced ACC neuronal firing in normal rats. In contrast, microdialysis of N-methyl-d-aspartate (NMDA) receptor antagonist AP5 had no effect on ACC neuronal firing in normal rats. However, AP5 produced 86% inhibition of ACC neuronal firing evoked by 50 mmHg CRD in the EA rats. In conclusion, ACC nociceptive transmissions are mediated by glutamate AMPA receptors in the control rats. ACC responses to CRD are enhanced in viscerally hypersensitive rats. The enhancement of excitatory glutamatergic transmission in the ACC appears to mediate this response. Furthermore, NMDA receptors mediate ACC synaptic responses after the induction of visceral hypersensitivity.

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