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Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAGCamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAGCamkIIα+ neurons.Significance Statement Neuropathic pain is clinically accompanied by anxiety. Both glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) and electroacupuncture (EA) have demonstrated analgesic properties. However, the efficacy of these interventions in addressing neuropathic pain and its concomitant anxiety has yet to be fully elucidated. In a mice model of spared nerve injury (SNI), we observed a decreased excitability of vlPAG CamkIIα neurons. Remarkably, EA treatment significantly enhanced the excitability of these neurons. Further, chemogenetic activation of vlPAGCamkIIα+ neurons not only resulted in analgesia but also mitigated anxiety-like behaviors in SNI mice, mirroring the effects observed with EA treatment. Conversely, inhibition of vlPAGCamkIIα+ neurons activity in naive mice reduced pain thresholds and induced anxiety-like behavior, while also negating the beneficial effects of EA. These findings provide novel insights into the mechanistic interplay between chronic neuropathic pain and anxiety, highlighting the therapeutic potential of targeting vlPAG glutamatergic neurons in these conditions.
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Recent studies have confirmed that pain memory is often accompanied by negative emotions. Electroacupuncture (EA) can block the retrieval of painful memories, thereby alleviating the associated negative behaviors. However, the underlying mechanism is poorly understood. This study revealed that the effect of EA on pain memory-induced negative behaviors is related to the mediation of GABAergic neuron activity and GABA receptor expression in the rostral anterior cingulate cortex (rACC). Previous studies have shown that the rACC is a crucial area for regulating nociceptive behaviors and negative emotions in pain memory models. The GABAergic neurons and receptors in the rACC are largely involved in pain sensation and related effects. However, the relationships among pain memory, GABAergic neurons and receptors in the rACC have not been investigated. In this study, we established a pain memory model via secondary plantar cross-injection of carrageenan and EA treatment. Using chemogenetic methods and behavioral assessments of pain and negative emotion, we found that early excitation of GABAergic neurons in the rACC blocked the recall of pain memories and reduced anxiety-like behaviors in pain memory model rats. Furthermore, pharmacological methods revealed that excitation of GABAA and GABAB receptors in the rACC blocks hyperpathia associated with pain memory and pain-induced anxiety-like behaviors, while inhibition of GABAA and GABAB receptors reverses these effects. These results suggest that EA may alleviate pain and associated anxiety-like behaviors related to pain memories through the activation of GABAergic neurons and excitation of GABAA and GABAB receptors in the rACC.
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Ansiedad , Modelos Animales de Enfermedad , Electroacupuntura , Neuronas GABAérgicas , Giro del Cíngulo , Hiperalgesia , Memoria , Dolor , Ratas Sprague-Dawley , Animales , Electroacupuntura/métodos , Giro del Cíngulo/metabolismo , Neuronas GABAérgicas/metabolismo , Ansiedad/terapia , Ansiedad/metabolismo , Masculino , Hiperalgesia/terapia , Hiperalgesia/metabolismo , Memoria/fisiología , Dolor/metabolismo , Receptores de GABA/metabolismo , Conducta Animal , RatasRESUMEN
Background: The prevalence of pain comorbid and anxiety/depression in clinical observations has been high, and the number of related publications has increased in recent years. Nevertheless, few studies have used bibliometric methods to analyze the scientific research on comorbid pain and depression/anxiety. The aim of this study was to systematically examine the trends in global scientific research on comorbid pain and depression/anxiety from 2012 to 2022. Methods: Papers published between 2012 and 2022 were identified in the Web of Science database. Publications that examined comorbid pain and depression/anxiety were included. The language was limited to English. CiteSpace, Excel and VOSviewer were used to analyze the volume of publications, countries, institutions, authors, cocited authors, and keywords. Results: A total of 30,290 papers met the inclusion criteria of the study. Using CiteSpace, VOSviewer and Excel, the results showed that the United States (10,614 publications), Harvard University (1195 publications), and Jensen, Mark P. (77 publications) were the most productive country, institution, and author, respectively. The hotspots and frontiers were "relationship between depression and pain", "gender differences in pain and depression/anxiety domains", "study of specific pain types with depression/anxiety", "treatment of pain combined with anxiety/depression", and "effects of COVID-19 on patients with pain combined with depression/anxiety". Conclusion: These findings indicate a growing interest in the field of comorbid pain and depression/anxiety. The research has been broad and deep, but there is still much room for growth. Furthermore, there is a need for more mature global collaborative networks as well as more high-quality research results in the future.
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Pain-related aversive memory is common in chronic pain patients. Electroacupuncture has been demonstrated to block pain-related aversive memory. The insular cortex is a key region closely related to aversive behaviors. In our study, a potential mechanism underlying the effect of electroacupuncture treatment on pain-related aversive memory behaviors relative to the insular cortex was investigated. Our study used the chemogenetic method, pharmacological method, electroacupuncture intervention, and behavioral detection. Our study showed that both inhibition of gamma-aminobutyric acidergic neurons and activation of the kappa opioid receptor in the insular cortex blocked the pain-related aversive memory behaviors induced by 2 crossover injections of carrageenan in mice; conversely, both the activation of gamma-aminobutyric acidergic neurons and inhibition of kappa opioid receptor in the insular cortex play similar roles in inducing pain-related aversive memory behaviors following 2 crossover injections of carrageenan. In addition, activation of gamma-aminobutyric acidergic neurons in the insular cortex reversed the effect of kappa opioid receptor activation in the insular cortex. Moreover, electroacupuncture effectively blocked pain-related aversive memory behaviors in model mice, which was reversed by both activation of gamma-aminobutyric acidergic neurons and inhibition of kappa opioid receptor in the insular cortex. The effect of electroacupuncture on blocking pain-related aversive memory behaviors may be related to the activation of the kappa opioid receptor and inhibition of gamma-aminobutyric acidergic neurons in the insular cortex.
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Dolor Crónico , Electroacupuntura , Ratones , Humanos , Animales , Receptores Opioides kappa/metabolismo , Corteza Insular , Carragenina/toxicidad , Neuronas GABAérgicas/fisiología , Ácido gamma-Aminobutírico/farmacología , Enfermedad Crónica , RecurrenciaRESUMEN
Pain memory is commonly considered an underlying cause of chronic pain and is also responsible for a range of anxiety. Electroacupuncture (EA) has been shown to ameliorate pain memories and exert anti-anxiety effects. Previous research has indicated that GABAergic neurons and/or GABA receptors (GABARs) in the midcingulate cortex (MCC) have potential associations with chronic pain and anxiety. However, there is no known empirical research that has specifically studied the effects of EA on the GABAergic system in the MCC. Here, we used cross-injection of carrageenan to establish the pain memory rats model. Immunofluorescence were used to detect the excitability of GABAergic neurons within MCC. Von Frey filament, elevated zero maze, and open field tests were used to measure mechanical allodynia and anxiety-like behaviors, combined with chemogenetic and pharmacologic technologies. Finally, this study provides evidence that pain memories contribute to generalized negative emotions and that downregulating the activity of GABAergic neurons within MCC could block pain memories and reverse anxiety emotion. Specifically, GABABR is involved in pain memory and related anxiety-like behaviors. Activation of GABAergic neurons in the MCC did not reverse the effects of EA on pain memories and related anxiety-like behaviors, whereas these effects could be reversed by a GABABR agonist. These findings highlight the functional significance of GABABR in the EA-mediated attenuation of pain memories and related anxiety-like behaviors in rats.
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Dolor Crónico , Electroacupuntura , Ratas , Animales , Receptores de GABA-B , Ansiedad/terapia , Ácido gamma-AminobutíricoRESUMEN
Late-onset major depressive disorder (LOD) increases the risk of disability and suicide in elderly patients. However, the complex pathological mechanism of LOD still remains unclear. We selected 10 LOD patients and 12 healthy control samples from the GSE76826 dataset for statistical analysis. Under the screening criteria, 811 differentially expressed genes (DEGs) were screened. We obtained a total of two most clinically significant modules through the weighted gene co-expression network analysis (WGCNA). Functional analysis of the genes in the most clinically significant modules was performed to explore the potential mechanism of LOD, followed by protein-protein interaction (PPI) analysis and hub gene identification in the core area of the PPI network. Furthermore, we identified immune infiltrating cells using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm between healthy subjects and LOD patients with the GSE98793 dataset. Next, six hub genes (CD27, IL7R, CXCL1, CCR7, IGLL5, and CD79A) were obtained by intersecting hub genes with DEGs, followed by verifying the diagnostic accuracy with the receiver operating characteristic curve (ROC). In addition, we constructed the least absolute shrinkage and selection operator (LASSO) regression model for hub gene cross-validation. Finally, we found that CD27 and IGLL5 were good diagnostic indicators of LOD, and CD27 may be the key gene of immune function change in LOD. In conclusion, our research shows that the changes in the immune function may be an important mechanism in the development of LOD, which can provide some guidance for the related research of LOD in the future.
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Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4-L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε-TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system.
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Chronic pain is regarded to be one of the common and refractory diseases to cure in the clinic. One hundred Hz electroacupuncture (EA) is commonly used for inflammatory pain and 2 Hz for neuropathic pain possibly by modulating the transient receptor potential vanilloid subtype 1 (TRPV1) or the purinergic P2X3 related pathways. To clarify the mechanism of EA under various conditions of pathological pain, rats received a subcutaneous administration of complete Freund's adjuvant (CFA) for inflammatory pain and spared nerve injury (SNI) for neuropathic pain. The EA was performed at the bilateral ST36 and BL60 1 d after CFA or SNI being successfully established for 3 consecutive days. The mechanical hyperalgesia test was measured at baseline, 1 d after model establishment, 1 d and 3 d after EA. The co-expression changes, co-immunoprecipitation of TRPV1 and P2X3, and spontaneous pain behaviors (SPB) test were performed 3 d after EA stimulation. One hundred Hz EA or 2Hz EA stimulation could effectively down-regulate the hyperalgesia of CFA or SNI rats. The increased co-expression ratio between TRPV1 and P2X3 at the dorsal root ganglion (DRG) in two types of pain could be reduced by 100Hz or 2Hz EA intervention. While 100Hz or 2Hz EA was not able to eliminate the direct physical interaction between TRPV1 and P2X3. Moreover, EA could significantly inhibit the SPB induced by the co-activation of peripheral TRPV1 and P2X3. All results indicated that EA could significantly reduce the hyperalgesia and the SPB, which was partly related to inhibiting the co-expression and indirect interaction between peripheral TRPV1 and P2X3.
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Electroacupuntura , Ganglios Espinales/metabolismo , Hiperalgesia/terapia , Neuralgia/terapia , Receptores Purinérgicos P2X3/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Modelos Animales de Enfermedad , Ganglios Espinales/fisiopatología , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Masculino , Neuralgia/metabolismo , Neuralgia/fisiopatología , Umbral del Dolor , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
OBJECTIVE: To systematically evaluate the efficacy and safety of conventional therapy combined with moxibustion in the treatment of chronic obstructive pulmonary disease (COPD) in stable phase based on Meta-analysis medicine. METHODS: The randomized controlled trials (RCTs) of moxibustion as adjuvant therapy for COPD were retrieved from the databases of CNKI, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library and Ebsco. RevMan5.3 software was used for Meta analysis, and the quality of evidence was evaluated according to GRADE standards. RESULTS: A total of 16 RCTs were included, involving 1425 patients. The results of Meta-analysis showed that: compared with the conventional treatment, â the adjuvant therapy with moxibustion had advantages in reducing the number of acute exacerbations [MD=-0.31, 95%CI:-0.49--0.13, P=0.0006]; â¡the adjuvant therapy with moxibustion improved lung function significantly [FEV1% (MD=4.00, 95%CI:2.63-5.37, P<0.000 01) and FEV1/FVC (MD=3.56, 95%CI:1.69-5.43, P=0.000 2)]; â¢the adjuvant therapy with moxibustion could extend the 6 min walking distance (6WMD) (MD=35.00, 95%CI:18.02-51.99, P<0.000 1); â£the adjuvant therapy with moxibustion could improve the modified British Medical Research Council breathing questionnaire (mMRC) classification significantly (MD=-0.62, 95%CI:-1.18--0.05, P=0.03); â¤no adverse reaction was reported in the included literature. CONCLUSION: The efficacy of moxibustion as adjuvant therapy for COPD in stable phase is better than that of simple conventional therapy. Due to insufficient clinical evidence and the limitations of this study, clinical safety is unclear and further evidence is needed to support the results.
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Moxibustión , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Stable angina pectoris (SAP) is a global health challenge. Multiple previous systematic reviews (SRs) have been conducted to assess the effectiveness of acupuncture and related therapies on SAP. We will carry out a comprehensive overview to map, synthesize, and assess the all the available evidence of acupuncture and related therapies on SAP. METHODS: We will search 7 databases, including China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CBM), WanFang Database, the Cochrane Library, PubMed, EMbase, MEDLINE. SRs and meta-analyses (MAs) of acupuncture and related therapies on SAP will be screened for eligibility. Systematic reviews, qualification evaluation, data extraction, methodological quality, and evidence quality evaluation will be conducted in pairs. The outcomes of interest include: frequency of angina attack, changes in nitroglycerin use, intensity of anginal pain, depression assessment, changes of the electrocardiogramme (ECG), anxiety assessment, results of the Six-Minute Walk Test (6-MWT), overall effectiveness, the Seattle Angina Questionnaire (SAQ), and adverse events. Where appropriate, the evidence will be synthesized based on the outcomes and patient subgroups. RESULTS: This overview will be published in a peer-reviewed journal. CONCLUSION: This overview is expected to provide a reliable and valuable evidence of acupuncture for treating SAP. ETHICS AND COMMUNICATION: Given that this is an overview of published research, patient consent and ethical approval are not needed. The findings of this study will be disseminated through conference presentations and publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020164466.
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Terapia por Acupuntura , Angina Estable/terapia , Humanos , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Musculoskeletal injuries (MSDs) have become a major public health problem worldwide. Current diagnosis techniques for MSDs are often associated with radiation exposure, expensive cost, or contraindication. Infrared thermography (IRT) is becoming a proposed tool to assist in diagnosing MSDs, but current evidence is inconclusive. Thus, herein we aimed to evaluate the diagnostic accuracy of IRT for MSDs. METHODS: We will search EMBASE, MEDLINE, EBSCO, Cochrane Library, SCOPUS, Web of Science, CNKI, SinoMed, and Wangfang. Two researchers will independently screen eligible studies. Study quality will be evaluated based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data synthesis will be completed using STATA 14.0 software. A bivariate random-effects analysis will be utilized to estimate the pooled estimation of the diagnostic odds ratio (DOR) and the summary receiver operating characteristics (SROC) curve. Subgroup analyses will be performed to determine heterogeneity sources. RESULTS: This systematic review and meta-analysis will provide reliable evidence about the diagnostic accuracy of IRT for MSDs. CONCLUSION: The conclusion of this study will be published in a peer-reviewed journal. ETHICS AND COMMUNICATION: Given that this is a systematic review of published research, patient consent and ethical approval are not relevant. The findings of this study will be disseminated through conference presentations and publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020184867.
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Rayos Infrarrojos , Sistema Musculoesquelético/lesiones , Termografía/métodos , Heridas y Lesiones/diagnóstico , Diagnóstico Diferencial , Humanos , Metaanálisis como Asunto , Oportunidad Relativa , Curva ROC , Proyectos de Investigación , Sensibilidad y Especificidad , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Acute pain can transition to chronic pain, presenting a major clinical challenge. Electroacupuncture (EA) can partly prevent the transition from acute to chronic pain. However, little is known about the mechanisms underlying the effect of EA. This study investigated the effect of EA on pain transition and the activation of metabotropic glutamate receptor 5 (mGluR5)-protein kinase C epsilon (PKCε) signaling pathway in the dorsal root ganglia (DRG). METHODS: The hyperalgesic priming model was established by the sequential intraplantar injection of carrageenan (1%, 100 µL) and prostaglandin E2 (PGE2) into the left hind paw of rats. EA treatment (2/100 Hz, 30 min, once/day) was applied at bilateral Zusanli (ST36) and Kunlun (BL60) acupoints in rats. Von Frey filaments were used to investigate the mechanical withdrawal threshold (MWT) at different time points. The protein expression levels of mGluR5 and PKCε in the ipsilateral L4-L6 DRGs of rats were detected by Western blot. Some pharmacological experiments were performed to evaluate the relationship between mGluR5, PKCε and the MWT. It was also used to test the effects of EA on the expression levels of mGluR5 and PKCε and changes in the MWT. RESULTS: Sequential injection of carrageenan and PGE2 significantly decreased the MWT of rats and up-regulated the expression level of mGluR5 and PKCε in the ipsilateral L4-L6 DRGs. EA can reverse the hyperalgesic priming induced by sequential injection of carrageenan/PGE and down-regulate the protein expression of mGluR5 and PKCε. Glutamate injection instead of PGE2 can mimic the hyperalgesic priming model. Pharmacological blocking of mGluR5 with specific antagonist MTEP can prevent the hyperalgesic priming and inhibit the activation of PKCε in DRGs. Furthermore, EA also produced analgesic effect on the hyperalgesic priming rats induced by carrageenan/mGluR5 injection and inhibited the high expression of PKCε. Sham EA produced none analgesic and regulatory effect. CONCLUSION: EA can regulate pain transition and it may relate with its inhibitory effect on the activation of mGluR5-PKCε signaling pathway in the DRGs.
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OBJECTIVE: Electroacupuncture (EA) is reported effective in alleviating pain-related emotion; however, the underlying mechanism of its effects still needs to be elucidated. The NPS-NPSR system has been validated for the involvement in the modulation of analgesia and emotional behavior. Here, we aimed to investigate the role of the NPS-NPSR system in the anterior cingulate cortex (ACC), hypothalamus, and central amygdala (CeA) in the use of EA to relieve affective pain modeled by complete Freund's adjuvant- (CFA-) evoked conditioned place aversion (C-CPA). Materials and Methods. CFA injection combined with a CPA paradigm was introduced to establish the C-CPA model, and the elevated O-maze (EOM) was used to test the behavioral changes after model establishment. We further explored the expression of NPS and NPSR at the protein and gene levels in the brain regions of interest by immunofluorescence staining and quantitative real-time PCR. RESULTS: We observed that EA stimulation delivered to the bilateral Zusanli (ST36) and Kunlun (BL60) acupoints remarkably inhibited sensory pain, pain-evoked place aversion, and anxiety-like behavior. The current study showed that EA significantly enhanced the protein expression of this peptide system in the ACC and hypothalamus, while the elevated expression of NPSR protein alone was just confined to the affected side in the CeA. Moreover, EA remarkably upregulated the mRNA expression of NPS in CeA, ACC, and hypothalamus and NPSR mRNA in the hypothalamus and CeA. CONCLUSIONS: These data suggest the effectiveness of EA in alleviating affective pain, and these benefits may at least partially be attributable to the upregulation of the NPS-NPSR system in the ACC and hypothalamus.
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BACKGROUND: The neuropeptide S/Neuropeptide S receptor (NPS/NPSR) system is involved in the regulation of anxiety in rodents. Chronic inflammation can induce anxiety. Our lab has observed that electroacupuncture (EA) has a beneficial effect on chronic inflammatory pain and pain-related anxiety; however, the mechanism should be further clarified. In the present study, we used an inflammatory pain model to investigate the role of the NPS/NPSR system in the anterior cingulate cortex (ACC) in the analgesic and antianxiety effects of EA. RESULTS: In an inflammatory pain model, the paw withdrawal thresholds (PWTs) were decreased, pain-related anxiety-like behaviors were induced, and the ipsilateral protein expression of NPS and NPSR was decreased in the ACC. EA stimulation increased the PWTs, reduced pain-related anxiety-like behavior, and enhanced the ipsilateral protein expression of NPS and NPSR in the ACC. NPS microinjection increased the PWTs and decreased pain-related anxiety-like behaviors. Furthermore, an NPSR inhibitor combined with EA reversed the effect of EA on the PWTs and pain-related anxiety-like behaviors. CONCLUSIONS: Our results suggest that EA suppresses pain and pain-related anxiety-like behavior of chronic inflammation in rats by increasing the expression of the NPS/NPSR system in the ACC.
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Ansiedad/metabolismo , Electroacupuntura , Giro del Cíngulo/metabolismo , Inflamación/metabolismo , Neuropéptidos/metabolismo , Dolor/metabolismo , Receptores de Neuropéptido/metabolismo , Animales , Ansiedad/complicaciones , Inflamación/complicaciones , Masculino , Dolor/complicaciones , Umbral del Dolor , Ratas Sprague-DawleyRESUMEN
Protein kinase Cε (PKCε) is a transforming oncogene and plays an important role in many cellular processing. In the present paper, we review the development of experimental researches on the acute-chronic pain transformation. Results indicated that prostaglandin E2 (PGE2) / EP1 receptor-Gq-PKCε is an important signaling pathway to modulate chronic pain in peripheral dorsal root ganglion (DRG) neurons, and also plays a role in the later stage of hyperalgesia during transformation from acute to chronic pain. PKCε in DRG neurons induces mechanical and thermal hypersensitivity respectively by over expression of transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin-1 (TRPA1), further mediating the transformation from acute to chronic pain. Whereas, PGE2-evoked activation of EP1-Gq-PKCε signaling may be the key link in initiating the pain translation process through regulating downstream TRPA1 and TRPV1. Electroacupuncture (EA) has been used to effectively relieving various types of acute and chronic pain for decades, and can significantly inhibit the expression of PKCε and its upstream and downstream molecules. Therefore, it can be inferred that there exists a possibility of EA interventions in interfering the transformation from acute to chronic pain by regulating peripheral PKCε signaling pathway.
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Dolor Crónico , Electroacupuntura , Animales , Humanos , Hiperalgesia , Proteína Quinasa C-epsilon , Ratas , Ratas Sprague-Dawley , Canales Catiónicos TRPVRESUMEN
Chronic inflammatory pain is one of the most common complaints that seriously affects patients' quality of life. Previous studies have demonstrated that the analgesic effect of electroacupuncture (EA) stimulation on inflammatory pain is related to its frequency. In this study, we focused on whether the analgesic effects of EA are related to the period of stimulation. Purinergic receptor P2X3 (P2X3) is involved in the pathological process underlying chronic inflammatory pain and neuropathic pain. We hypothesized that 100 Hz EA stimulation alleviated Freund's complete adjuvant (CFA) induced inflammatory pain via regulating P2X3 expression in the dorsal root ganglion (DRG) and/or spinal cord dorsal horn (SCDH). We also assumed that the analgesic effect of EA might be related to the period of stimulation. We found that both short-term (three day) and long-term (14 day) 100 Hz EA stimulation effectively increased the paw withdrawal threshold (PWT) and reversed the elevation of P2X3 in the DRG and SCDH of CFA rats. However, the analgesic effects of 100 Hz EA were not dependent on the period of stimulation. Moreover, P2X3 inhibition or activation may contribute to or attenuate the analgesic effects of 100 Hz EA on CFA-induced inflammatory pain. This result indicated that EA reduced pain hypersensitivity through P2X3 modulation.
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Electroacupuntura/métodos , Adyuvante de Freund , Manejo del Dolor/métodos , Dolor/inducido químicamente , Receptores Purinérgicos P2X3/análisis , Animales , Ganglios Espinales/patología , Inflamación/inducido químicamente , Inflamación/patología , Inflamación/terapia , Masculino , Dolor/patología , Ratas Sprague-Dawley , Asta Dorsal de la Médula Espinal/patologíaRESUMEN
OBJECTIVE: To observe the effect of electroacupuncture (EA)on mechanical pain transition and content of protein kinase C epsilon(PKCε)in dorsal root ganglia (DRG) in inflammatory articular pain ratsï¼so as to explore its peripheral mechanism underlying relieving transition from acute to chronic pain. METHODS: 1)In the first part of the present studyï¼male SD rats were equally randomized into blank controlï¼sham hyperalgesic priming(HP), and real HP groups(nï¼6 in each). The HP model was established by subcutaneous injection of 1% carrageenan (100 µL) into the left hind paw (the first injection)ï¼followed by injection of PGE 2 (100 ng/25 µL, the second injection) into the dorsum pedis of the same hind paw 7 days after the first injection. The mechanical withdrawal threshold (MWT) of the ipsilateral paw was detected before and 4, 24, 48, 72 h, and 7 d after the first injectionï¼and 1, 4, 24 and 48 h after the second injection. 2) In the second partï¼SD rats were randomly divided into sham-HPï¼real HPï¼sham-EA and EA groups(nï¼6 in each). The sham-HP and HP models were made in the same way as those in the first part. Bilateral "Zusanli"(ST 36)and "Kunlun"(BL 60)were punctured with filiform needles and also stimulated with electrical currentï¼2 Hz/100 Hzï¼0.5ï¼1.5 mA(0.5 mA increase per 10 min)for 30 minï¼1 time/d from the 1st carrageenan injection on till the end of the experiments. PKCε protein expression in the L 4ï¼L 6 DRGs was assayed by Western blot 48 h after the second injection. RESULTS: 1)In the first part of the studyï¼compared with the sham-HP groupï¼the MWT at 4, 24ã48 h after carrageenan injection and 4, 24 and 48 h after PGE 2 injection were significantly decreased in the HP model group(P<0.01). 2)In the second partï¼compared with the HP groupï¼the MWT at 24ã48 and 72 h after carrageenan injection, and 24 and 48 h after PGE 2 injection were significantly up-regulated in the EA group(P<0.05ï¼P<0.01). 3)The relative content of PKCε in the DRGs(L 4ï¼L 6)was significantly higher in the HP group than in the sham-HP group(P<0.01)ï¼but considerably lower in the EA group than in the HP group (P<0.01)ï¼. CONCLUSION: EA has a good effect on pain conversion in inflammatory joint pain ratsï¼which may be related to its effect in down-regulating the PKCε level in the ipsilateral lumbar DRGs.
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Electroacupuntura , Puntos de Acupuntura , Animales , Ganglios Espinales , Hiperalgesia , Masculino , Proteína Quinasa C-epsilon , Ratas , Ratas Sprague-DawleyRESUMEN
Professor FANG Jianqiao's clinical experience in the treatment of primary cervical dystonia based on the syndrome differentiation of TCM was explored preliminarily. Based on the disease identification of western medicine and the syndrome differentiation of TCM, in combination with the differentiations of meridians and collaterals of acupuncture, Professor FANG proposes the three-dimensional system of diagnosis and treatment of acupuncture, named "disease differentiation, TCM syndrome differentiation and meridian differentiation". Regarding the diagnosis and treatment of primary cervical dystonia, the physical examination of nerve system, TCM syndrome differentiation and meridian differentiation are equally important. It is pointed out that the key pathogenesis of the disease is qi and blood obstruction and the malnutrition in the muscle regions of meridians. Hence, the treating principle is proposed as eliminating the exogenous pathogens, regulating qi and blood and unblocking the muscle regions of meridians. Professor FANG also stresses that the affected sites and the factors of dystonia should be considered in acupuncture treatment. The local points are mainly those adjacent to the responsible muscles with the motor disturbance in the neck region. "Xinshe" point (Extra) is taken as the empirical point. The distal points are selected in accordance with the three-dimensional system of diagnosis and treatment. At the same time, the percutaneous acupoint electric stimulation is applied to the starting and ending points or the conjunctive points of the affected muscles, acting on regulating qi, nourishing blood and promoting the circulation in meridians and collaterals.