scholarly journals Chronic Constriction Injury Induced Long-Term Changes in Spontaneous Membrane-Potential Oscillations in Anterior Cingulate Cortical Neurons in Vivo

2013 ◽  
Vol 5;16 (5;9) ◽  
pp. E577-E589
Author(s):  
Ying-Wei Wang
Keyword(s):  
Neuropathic Pain ◽  
Membrane Potential ◽  
Sciatic Nerve ◽  
Anterior Cingulate Cortex ◽  
Nerve Injury ◽  
Chronic Constriction Injury ◽  
Anterior Cingulate ◽  
Spontaneous Pain ◽  
Pain Hypersensitivity

Background: Neuropathic pain induction by nerve injury has been shown by in vitro studies to be accompanied by synaptic strengthening in the anterior cingulate cortex (ACC) and has been shown by pharmacological studies in vivo to be prevented by blocking N-methyl-D-aspartate (NMDA) receptor-dependent ACC plasticity. These findings indicate that ACC neurons undergo nerve injury-induced synaptic modifications and further raise a new question about neuropathic pain-associated changes in neuronal activity in the ACC in vivo, particularly spontaneous neuronal oscillations – a process believed to be fundamental for many forms of brain function. Objective: In this study, we examined the change of spontaneous membrane-potential (MP) oscillations in the ACC in vivo in a neuropathic pain animal model of chronic constriction injury (CCI), which may account for neuropathic pain development, as well as pain hypersensitivity and spontaneous pain. Study Design: Experimental trial in rats. Methods: Neuropathic pain rats were produced by CCI surgery on the common sciatic nerve. Neuropathic pain-related behaviors were accessed by evoked responses to both mechanical and thermal stimuli, as well as spontaneous pain indicated by spontaneous foot lifting. In vivo wholecell recording was performed in both control and neuropathic pain rats under anaesthesia. MP and action-potential (AP) changes of layer II/III ACC pyramidal cells were measured in current-clamp mode. The level of anaesthesia was evaluated by monitoring respiratory and heart rates in some experiments. Results: Within 7 to 14 days after CCI surgery, the frequency of MP oscillations of ACC neurons was found to be significantly higher than that in control rats. Such an increase in oscillation frequency after surgery was not due to periphery transmission via the sciatic nerve subjected to CCI surgery and was indicated to be accounted for by neuronal modifications in the central nervous system. Furthermore, this increase was found to result in a higher overall level of MP excitation as well as an increase in spontaneous AP firing. Limitations: Our findings in MP and AP changes were obtained in anaesthetized brains; this issue remains to be further examined by using whole-cell recording in awake behaving animals. Conclusions: Neuropathic pain is accompanied by the increase in rates of spontaneous oscillations of ACC neurons. This change may be critical for neuropathic pain development, as well as pain hypersensitivity and spontaneous pain in neuropathic pain animals. Key Words: Neuropathic pain, anterior cingulate cortex, spontaneous activity, neuronal oscillation, chronic constriction injury

scholarly journals A transcriptomic analysis of neuropathic pain in the anterior cingulate cortex after nerve injury

Bioengineered ◽  
2022 ◽  
Vol 13 (2) ◽  
pp. 2058-2075
Author(s):  
Yu Zhang ◽  
Shiwei Jiang ◽  
Fei Liao ◽  
Zhifeng Huang ◽  
Xin Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Nerve Injury ◽  
Cingulate Cortex ◽  
Transcriptomic Analysis ◽  
Anterior Cingulate

scholarly journals Dynamic effects of TNF-α on synaptic transmission in mice over time following sciatic nerve chronic constriction injury

2013 ◽  
Vol 110 (7) ◽  
pp. 1663-1671 ◽  
Author(s):  
Hongmei Zhang ◽  
Haijun Zhang ◽  
Patrick M. Dougherty
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Chronic Constriction Injury ◽  
Synaptic Signaling ◽  
Tnf Α ◽  
Over Time

Nerve injury-induced central sensitization can manifest as an increase in excitatory synaptic transmission and/or as a decrease in inhibitory synaptic transmission in spinal dorsal horn neurons. Cytokines such as tumor necrosis factor-α (TNF-α) are induced in the spinal cord under various injury conditions and contribute to neuropathic pain. In this study we examined the effect of TNF-α in modulating excitatory and inhibitory synaptic input to spinal substantia gelatinosa (SG) neurons over time in mice following chronic constriction injury (CCI) of the sciatic nerve. Whole cell patch-clamp studies from SG neurons showed that TNF-α enhanced overall excitability of the spinal cord early in time following nerve injury 3 days after CCI compared with that in sham control mice. In contrast, the effects of TNF were blunted 14 days after CCI in nerve-injured mice compared with sham surgery mice. Immunohistochemical staining showed that the expression of TNF-α receptor 1 (TNFR1) was increased at 3 days but decreased at 14 days following CCI in the ipsilateral vs. the contralateral spinal cord dorsal horn. These results suggest that TNF-α acting at TNFR1 is important in the development of neuropathic pain by facilitating excitatory synaptic signaling in the acute phases after nerve injury but has a reduced effect on spinal neuron signaling in the later phases of nerve injury-induced pain. Failure of the facilatory effects of TNF-α on excitatory synaptic signaling in the dorsal horn to resolve following nerve injury may be an important component in the transition between acute and chronic pain conditions.

scholarly journals Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Songxue Su ◽  
Mengqi Li ◽  
Di Wu ◽  
Jing Cao ◽  
Xiuhua Ren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Anterior Cingulate Cortex ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Anterior Cingulate ◽  
Anxiety And Depression ◽  
Gene Transcript

Chronic neuropathic pain caused by nerve damage is a most common clinical symptom, often accompanied by anxiety- and depression-like symptoms. Current treatments are very limited at least in part due to incompletely understanding mechanisms underlying this disorder. Changes in gene expression in the dorsal root ganglion (DRG) have been acknowledged to implicate in neuropathic pain genesis, but how peripheral nerve injury alters the gene expression in other pain-associated regions remains elusive. The present study carried out strand-specific next-generation RNA sequencing with a higher sequencing depth and observed the changes in whole transcriptomes in the spinal cord (SC), anterior cingulate cortex (ACC), and amygdala (AMY) following unilateral fourth lumbar spinal nerve ligation (SNL). In addition to providing novel transcriptome profiles of long non-coding RNAs (lncRNAs) and mRNAs, we identified pain- and emotion-related differentially expressed genes (DEGs) and revealed that numbers of these DEGs displayed a high correlation to neuroinflammation and apoptosis. Consistently, functional analyses showed that the most significant enriched biological processes of the upregulated mRNAs were involved in the immune system process, apoptotic process, defense response, inflammation response, and sensory perception of pain across three regions. Moreover, the comparisons of pain-, anxiety-, and depression-related DEGs among three regions present a particular molecular map among the spinal cord and supraspinal structures and indicate the region-dependent and region-independent alterations of gene expression after nerve injury. Our study provides a resource for gene transcript expression patterns in three distinct pain-related regions after peripheral nerve injury. Our findings suggest that neuroinflammation and apoptosis are important pathogenic mechanisms underlying neuropathic pain and that some DEGs might be promising therapeutic targets.

Attenuation of Neuropathic Pain by Inhibiting Electrical Synapses in the Anterior Cingulate Cortex

2016 ◽  
Vol 124 (1) ◽  
pp. 169-183 ◽  
Author(s):  
Zhi-Yu Chen ◽  
Feng-Yan Shen ◽  
Lai Jiang ◽  
Xuan Zhao ◽  
Xiao-Lu Shen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Synaptic Plasticity ◽  
Anterior Cingulate Cortex ◽  
Nerve Injury ◽  
Cingulate Cortex ◽  
Gamma Oscillations ◽  
Anterior Cingulate ◽  
Neuronal Oscillations ◽  
Electrical Synapses

Abstract Background Synaptic mechanisms and neuronal oscillations have been proposed to be responsible for neuropathic pain formation. Many studies have also highlighted the important role of electrical synapses in synaptic plasticity and in neuronal oscillations. Thus, electrical synapses may contribute to neuropathic pain generation. However, previous studies have primarily focused on the role of chemical synapses, while ignoring the role of electrical synapses, in neuropathic pain generation. Methods The authors adopted microinjection, RNA interference techniques, and behavioral tests to verify the link between connexin 36 (Cx36) and neuropathic pain. They also studied the selective Cx36 blocker mefloquine in rat chronic constriction injury and spared nerve injury model of neuropathic pain. Electrophysiologic recordings were used to further confirm the behavioral data. Results The authors found that Cx36, which constitutes the neuron–neuron electrical synapses, was up-regulated in the anterior cingulate cortex after nerve injury (n = 5). Meanwhile, Cx36-mediated neuronal oscillations in the gamma frequency range (30 to 80 Hz) (n = 7 to 8) and the neuronal synaptic transmission (n = 13 to 19) were also enhanced. Neuropathic pain was relieved by disrupting Cx36 function or expression in the anterior cingulate cortex. They also found that mefloquine, which are clinically used for treating malaria, affected gamma oscillations and synaptic plasticity, leading to a sustained pain relief in chronic constriction injury and spared nerve injury models (n = 7 to 12). Conclusion The electrical synapses blocker mefloquine could affect gamma oscillations and synaptic plasticity in the anterior cingulate cortex and relieve neuropathic pain. Cx36 may be a new therapeutic target for treating chronic pain.

Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKM  in the Anterior Cingulate Cortex

Science ◽  
2010 ◽  
Vol 330 (6009) ◽  
pp. 1400-1404 ◽  
Author(s):  
X.-Y. Li ◽  
H.-G. Ko ◽  
T. Chen ◽  
G. Descalzi ◽  
K. Koga ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Pain Hypersensitivity

scholarly journals Nitrous Oxide Persistently Alleviates Pain Hypersensitivity in Neuropathic Rats: A Dose-Dependent Effect

2015 ◽  
Vol 20 (6) ◽  
pp. 309-315 ◽  
Author(s):  
Meric Ben Boujema ◽  
Emilie Laboureyras ◽  
Jan Pype ◽  
Baptiste Bessière ◽  
Guy Simonnet
Keyword(s):  
Nitrous Oxide ◽  
Neuropathic Pain ◽  
Pain Relief ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Male Rats ◽  
Dependent Effect ◽  
Pain Hypersensitivity ◽  
Dose Dependent ◽  
Dose Dependent Effect

BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of theN-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury.OBJECTIVE: Using the chronic constriction injury of the sciatic nerve in male rats as a preclinical model of neuropathic pain, the first aim of the present study was to evaluate the lowest N2O concentration and the shortest time of N2O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N2O with gabapentin, a reference drug used in human neuropathic pain relief.METHODS: Changes in the nociceptive threshold were evaluated using the paw pressure vocalization test in rats.RESULTS: Among the various N2O concentrations tested, which ranged from 25% to 50%, only 50% N2O single exposure for 1 h 15 min induced a persistent (minimum of three weeks) and significant (60%) reduction in pain hypersensitivity. A single gabapentin dose (75 mg/kg to 300 mg/kg, intraperitoneally) induced an acute (1 h to 1 h 30 min) dose-dependent effect, but not a persistent effect such as that observed with N2O.CONCLUSIONS: These preclinical results suggest that N2O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies.

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