scholarly journals Effects and Mechanisms of Electroacupuncture on Chronic Inflammatory Pain and Depression Comorbidity in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hung-Yu Huang ◽  
Hsien-Yin Liao ◽  
Yi-Wen Lin
Keyword(s):  
Chronic Pain ◽  
Signaling Pathway ◽  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Chronic Inflammatory Pain ◽  
Calcium Calmodulin Dependent ◽  
Successful Induction ◽  
Dependent Protein ◽  
The Brain ◽  
Depression Disorder

Comorbidity of chronic pain and major depression disorder (MDD) are common diseases. However, the mechanisms of electroacupuncture (EA) and the responses of N-methyl-D-aspartate receptors in the brain remain unclear. Three injections of complete Freund's adjuvant (CFA) were administered to induce chronic inflammatory pain (CIP). EA was then performed once every other day from days 14 to 28. Behavior tests of chronic pain and depression were evaluated to make sure of the successful induction of comorbidity. We used Western blotting to analyze brain tissue from the prefrontal cortex (PFC), hippocampus, and hypothalamus for levels of phosphorylated N-methyl-D-aspartate receptor subunit 1 (pNR1), NR1, pNR2B, NR2B, and calcium/calmodulin-dependent protein kinase type II alpha isoform (pCaMKIIα). The mechanical hyperalgesia, thermal hyperalgesia, and depression were observed in the CIP group. Furthermore, decreased levels of N-methyl-D-aspartate receptors (NMDARs) were also noted. Not Sham EA but EA reversed chronic pain and depression as well as the decreased levels of NMDA in the signaling pathway. The CFA injections successfully induced a significant comorbidity model. EA treated the comorbidity by upregulating the NMDA signaling pathway in the PFC, hippocampus, and hypothalamus. Our results indicated significant mechanisms of comorbidity of chronic pain and MDD and EA-analgesia that involves the regulation of the NMDAR signaling pathway. These findings may be relevant to the evaluation and treatment of comorbidity of chronic pain and MDD.

scholarly journals Involvement of MrgprC in Electroacupuncture Analgesia for Attenuating CFA-Induced Thermal Hyperalgesia by Suppressing the TRPV1 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-13
Author(s):  
Ying-jun Liu ◽  
Xiao-xi Lin ◽  
Jian-qiao Fang ◽  
Fang Fang
Keyword(s):  
Chronic Pain ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Pain Modulation ◽  
Transient Receptor Potential Vanilloid ◽  
Chronic Inflammatory Pain ◽  
Transient Receptor

Mas-related G-protein-coupled receptor C (MrgprC) plays an important role in modulating chronic inflammatory pain. Electroacupuncture (EA) has a satisfactory analgesic effect on chronic pain. This study aimed to investigate the involvement of MrgprC and its transient receptor potential vanilloid 1 (TRPV1) pathway in EA analgesia in chronic inflammatory pain. Chronic inflammatory pain was induced by subcutaneously injecting complete Freund’s adjuvant (CFA) into the left hind paw. EA (2/100 Hz) stimulation was administered. MrgprC siRNAs were intrathecally administered to inhibit MrgprC expression, and bovine adrenal medulla 8-22 (BAM8-22) was used to activate MrgprC. The mechanical allodynia was decreased by EA significantly since day 3. The piled analgesic effect of EA was partially blocked by 6 intrathecal administrations of MrgprC siRNA. Both EA and BAM8-22 could downregulate the expression of TRPV1 and PKC in both the DRG and the SCDH. Both EA and BAM8-22 could also decrease the TRPV1 translocation and p-TRPV1 level in both the DRG and the SCDH. The effects of EA on PKCε, TRPV1 translocation, and p-TRPV1 in both the DRG and the SCDH were reversed by MrgprC siRNA. The results indicated that MrgprC played crucial roles in chronic pain modulation and was involved in EA analgesia partially through the regulation of TRPV1 function at the DRG and SCDH levels.

scholarly journals Activation State-Dependent Substrate Gating in Ca2+/Calmodulin-Dependent Protein Kinase II

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
D. E. Johnson ◽  
A. Hudmon
Keyword(s):  
Protein Kinase ◽  
Catalytic Domain ◽  
Intrinsic Property ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
State Dependent ◽  
Protein Kinase Ii ◽  
Dependent Protein ◽  
Substrate Phosphorylation ◽  
The Brain

Calcium/calmodulin-dependent protein kinase II (CaMKII) is highly concentrated in the brain where its activation by the Ca2+sensor CaM, multivalent structure, and complex autoregulatory features make it an ideal translator of Ca2+signals created by different patterns of neuronal activity. We provide direct evidence that graded levels of kinase activity and extent of T287(T286αisoform) autophosphorylation drive changes in catalytic output and substrate selectivity. The catalytic domains of CaMKII phosphorylate purified PSDs much more effectively when tethered together in the holoenzyme versus individual subunits. Using multisubstrate SPOT arrays, high-affinity substrates are preferentially phosphorylated with limited subunit activity per holoenzyme, whereas multiple subunits or maximal subunit activation is required for intermediate- and low-affinity, weak substrates, respectively. Using a monomeric form of CaMKII to control T287autophosphorylation, we demonstrate that increased Ca2+/CaM-dependent activity for all substrates tested, with the extent of weak, low-affinity substrate phosphorylation governed by the extent of T287autophosphorylation. Our data suggest T287autophosphorylation regulates substrate gating, an intrinsic property of the catalytic domain, which is amplified within the multivalent architecture of the CaMKII holoenzyme.

scholarly journals Galanin Receptor 2 Is Involved in Galanin-Induced Analgesic Effect by Activating PKC and CaMKII in the Nucleus Accumbens of Inflammatory Pain Rats

2021 ◽  
Vol 14 ◽  
Author(s):  
Mengnan Li ◽  
Xiaomin Zhang ◽  
Chongyang Li ◽  
Yanan Liu ◽  
Shuang Yang ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Protein Kinase ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Signaling Mechanism ◽  
Withdrawal Threshold ◽  
Calcium Calmodulin Dependent ◽  
Kinase C ◽  
Dependent Protein ◽  
Galanin Receptors

It has been reported that galanin has an analgesic effect via activating galanin receptors (GALRs). This study focused on the involvement of GALR2 in the galanin-induced analgesic effect and its signaling mechanism in the nucleus accumbens (NAc) of inflammatory rats. Animal models were established through injecting carrageenan into the plantar of rats’ left hind paw. The results showed that GALR2 antagonist M871 weakened partially the galanin-induced increases in hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation in NAc of inflammatory rats. Moreover, the GALR2 agonist M1145 prolonged the HWL and HWT, while M871 blocked the M1145-induced increases in HWL and HWT. Western blotting showed that the phosphorylation of calcium/calmodulin-dependent protein kinase II (p-CaMKII) and protein kinase C (p-PKC) in NAc were upregulated after carrageenan injection, while p-PKC and p-CaMKII were downregulated after intra-NAc administration of M871. Furthermore, the CaMKII inhibitor KN93 and PKC inhibitor GO6983 attenuated M1145-induced increases in HWL and HWT in NAc of rats with inflammatory pain. These results prove that GALR2 is involved in the galanin-induced analgesic effect by activating CaMKII and PKC in NAc of inflammatory pain rats, implying that GALR2 agonists probably are potent therapeutic options for inflammatory pain.

scholarly journals Analgesic Effect of Moxibustion with Different Temperature on Inflammatory and Neuropathic Pain Mice: A Comparative Study

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Zhou ◽  
Ruxue Lei ◽  
Chuanyi Zuo ◽  
Yunqing Yue ◽  
Qin Luo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Spared Nerve Injury ◽  
Chronic Neuropathic Pain ◽  
Chronic Inflammatory Pain ◽  
Significant Difference ◽  
Different Temperatures

The aim of this study was to determine whether variation of temperature during moxibustion would generate division of analgesic effect. The moxibustion with different temperatures (37°C, 42°C, 47°C, and 52°C) was applied to ST36 acupoint for 30 minutes in chronic inflammatory or neuropathic pain mice. The analgesic effect was evaluated by thermal hyperalgesia test in chronic inflammatory pain and by mechanical allodynia in neuropathic pain, respectively. The results indicated that interventions of moxibustion with different temperature caused different analgesic effect on either chronic inflammatory induced by injection of complete Freund’s adjuvant (CFA) or neuropathic pain induced by spared nerve injury (SNI). In chronic inflammatory pain, different moxibustion temperature generated different intensity of analgesic effect: the higher the better. In chronic neuropathic pain, stronger analgesic effect was found in moxibustion with temperature 47°C or 52°C other than 37°C and 42°C. However, there is no significant difference displayed between moxibustion temperatures 47°C and 52°C or 37°C and 42°C. It implies that the temperature should be taken into account for moxibustion treatment to chronic inflammatory or neuropathic pain.

scholarly journals Electroacupuncture Alleviates Experimental Chronic Inflammatory Pain by Inhibiting Calcium Voltage-Gated Channel-Mediated Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Jie Zhou ◽  
Ying Jin ◽  
Ruijie Ma ◽  
Hongyun Song ◽  
Qin Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Pain ◽  
Expression Profiles ◽  
Arachidonic Acid Metabolism ◽  
Receptor Interaction ◽  
Bioinformatics Analyses ◽  
Protein Coding ◽  
Chronic Inflammatory Pain ◽  
Gated Channel ◽  
Pathway Analyses

Background. Both experimental and clinical studies have shown that electroacupuncture (EA) administration ameliorates chronic inflammatory pain (CIP). However, the multifaceted mechanism underlying the effects of EA on CIP is poorly understood. In this study, the mRNA transcriptome was used to study various therapeutic targets of EA. Methods. Using RNA-sequencing, protein-coding mRNA expression profiles of the L4-L5 dorsal root ganglion (DRG) were examined in the control (CN), complete Freund’s adjuvant- (CFA-) induced CIP, and EA-treated CIP groups. A series of bioinformatics analyses was performed; “EA-reversed upregulated genes with CIP” (up-DEGs) and “EA-reversed downregulated genes with CIP” (down-DEGs) were identified. Thereafter, based on up-DEGs and down-DEGs, biological functions and signaling pathways were enriched using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. Results. In total, 189 DEGs were identified, including 134 up- and 55 down-DEGs, which were enriched in arachidonic acid metabolism (rno00590), glutamatergic synapse (rno04724), serotonergic synapse (rno04726), FoxO signaling pathway (rno04068), insulin signaling pathway (rno04910), amyotrophic lateral sclerosis (rno05014), cholinergic synapse (rno04725), ECM-receptor interaction (rno04512), and choline metabolism in cancer (rno05231). Conclusion. We identified a few GOs, pathways, and genes that could play key roles in the amelioration of CIP by EA. Hence, this study may provide a theoretical basis for CIP amelioration by EA.

Far Infrared Emitted by Bioceramics Reduces Mechanical and Thermal Hyperalgesia in an Animal Model of Chronic Inflammatory Pain

2014 ◽  
Vol 20 (5) ◽  
pp. A33-A33
Author(s):  
Aline A. Emer ◽  
Francisco Jose Cidral-Filho ◽  
Fernanda Madeira ◽  
Bruna L. Turnes ◽  
Daniel F. Martins
Keyword(s):  
Animal Model ◽  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Far Infrared ◽  
Chronic Inflammatory Pain

scholarly journals CaMKIIβ in Neuronal Development and Plasticity: An Emerging Candidate in Brain Diseases

2020 ◽  
Vol 21 (19) ◽  
pp. 7272
Author(s):  
Olivier Nicole ◽  
Emilie Pacary
Keyword(s):  
Neuronal Plasticity ◽  
Neuronal Development ◽  
Brain Diseases ◽  
Dependent Protein Kinase ◽  
Potential Implication ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein ◽  
The Subject ◽  
The Brain ◽  
Intense Research

The calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous and central player in Ca2+ signaling that is best known for its functions in the brain. In particular, the α isoform of CaMKII has been the subject of intense research and it has been established as a central regulator of neuronal plasticity. In contrast, little attention has been paid to CaMKIIβ, the other predominant brain isoform that interacts directly with the actin cytoskeleton, and the functions of CaMKIIβ in this organ remain largely unexplored. However, recently, the perturbation of CaMKIIβ expression has been associated with multiple neuropsychiatric and neurodevelopmental diseases, highlighting CAMK2B as a gene of interest. Herein, after highlighting the main structural and expression differences between the α and β isoforms, we will review the specific functions of CaMKIIβ, as described so far, in neuronal development and plasticity, as well as its potential implication in brain diseases.

Calcium/calmodulin-dependent protein kinase IV signaling pathway is upregulated in experimental necrotizing enterocolitis

2020 ◽  
Vol 36 (3) ◽  
pp. 271-277
Author(s):  
Mashriq Alganabi ◽  
Haitao Zhu ◽  
Joshua S. O’Connell ◽  
George Biouss ◽  
Andrea Zito ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Necrotizing Enterocolitis ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein

scholarly journals The Effect of Electroacupuncture on PKMzeta in the ACC in Regulating Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Junying Du ◽  
Junfan Fang ◽  
Cun Wen ◽  
Xiaomei Shao ◽  
Yi Liang ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Protein Expression ◽  
Inflammatory Pain ◽  
Direct Evidence ◽  
Anterior Cingulate ◽  
Model Group ◽  
Pain Model ◽  
Chronic Inflammatory Pain ◽  
Withdrawal Threshold ◽  
Other Substances

Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA) has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta) has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC). We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT) and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560), PKMzeta, p-PKMzeta (T560), and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560) in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC.

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.

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