163 results on '"chronic inflammatory pain"'
Search Results
2. Solanesol alleviates CFA-induced chronic inflammatory pain via inhibition of proinflammatory cytokines in spinal glial cells
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Wang, Yuan-yuan, Li, Yi-fan, and Zhou, Zhen-feng
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- 2024
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3. Mechanism of action of Shaoyao-Gancao decoction in relieving chronic inflammatory pain via Sema3G protein regulation in the dorsal root ganglion
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Lin, Rong, Gu, Jun-Gang, Wang, Zhi-Fu, Zeng, Xiao-Xia, Xiao, Hong-Wei, Chen, Jin-Cheng, and He, Jian
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- 2024
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4. Kv3.1 Interaction with UBR5 Is Required for Chronic Inflammatory Pain.
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Zeng, Ying, Sun, Meng-Lan, Liu, Di, Huang, Yue, Xie, Shan, Zhao, Ya-Xuan, Wu, Zi-Xuan, Liu, Ya, Ma, Gan, Xie, Ling, Dang, Yu-Tao, Hao, Ling-Yun, Wang, Qi-Hui, Wang, Hong-Jun, Yang, Li, Xue, Zhou-Ya, and Pan, Zhi-Qiang more...
- Abstract
Chronic inflammatory pain caused by neuronal hyperactivity is a common and refractory disease. Kv3.1, a member of the Kv3 family of voltage-dependent K
+ channels, is a major determinant of the ability of neurons to generate high-frequency action potentials. However, little is known about its role in chronic inflammatory pain. Here, we show that although Kv3.1 mRNA expression was unchanged, Kv3.1 protein expression was decreased in the dorsal spinal horn of mice after plantar injection of complete Freund's adjuvant (CFA), a mouse model of inflammatory pain. Upregulating Kv3.1 expression alleviated CFA-induced mechanical allodynia and heat hyperalgesia, whereas downregulating Kv3.1 induced nociception-like behaviors. Additionally, we found that ubiquitin protein ligase E3 component n-recognin 5 (UBR5), a key factor in the initiation of chronic pain, binds directly to Kv3.1 to drive its ubiquitin degradation. Intrathecal injection of the peptide TP-CH-401, a Kv3.1 ubiquitination motif sequence, rescued the decrease in Kv3.1 expression and Kv currents through competitive binding to UBR5, and consequently attenuated mechanical and thermal hypersensitivity. These findings demonstrate a previously unrecognized pathway of Kv3.1 abrogation by UBR5 and indicate that Kv3.1 is critically involved in the regulation of nociceptive behavior. Kv3.1 is thus a promising new target for treating inflammatory pain. [ABSTRACT FROM AUTHOR] more...- Published
- 2025
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5. Role of Vitamin D Status and Alterations in Gut Microbiota Metabolism in Fibromyalgia-Associated Chronic Inflammatory Pain.
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Saija, Caterina, Bertuccio, Maria Paola, Scoglio, Alberto, Macaione, Vincenzo, Cacciola, Francesco, Micalizzi, Giuseppe, Caccamo, Daniela, Muscoli, Carolina, and Currò, Monica
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VITAMIN D ,GUT microbiome ,INTERLEUKIN-17 ,CHRONIC pain ,DYSBIOSIS - Abstract
Background/Objectives: Several studies suggest gut microbiota metabolites as important immuno-modulators in inflammatory pain. We aimed to investigate the relationship between vitamin D status and gut dysbiosis markers in fibromyalgia (FM)-associated chronic inflammation. Methods: Blood samples were collected from sixty-eight female FM patients (49.9 ± 12.35 years). Pain intensity was assessed by FIQ-R. The serum levels of the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-17, IFN-γ, as well as those of vitamin D (25(OH)D3) and the kynurenine/tryptophan ratio (Kyn/Trp) were determined by ELISA and HPLC, respectively. The plasma levels of the SCFAs acetate, butyrate, and propionate were detected by GC-MS. Results: A mean FIQ-R score indicated that the patients could be classified as having moderate FM. The mean levels of all cytokines, but IL-6 and IL-1β, were higher than the normal reference values. The highest concentrations of cytokines were observed in patients showing the highest FIQ-R scores and the lowest 25(OH)D3 levels. Deficient levels of acetate were found paralleled by an increase in Kyn/Trp. The highest acetate concentrations were detected in patients with the lowest FIQ-R scores and 25(OH)D3 levels. Significantly negative correlations were found between 25(OH)D3 concentrations and FIQ-R scores (p = 0.007) as well as IL-17 levels (p = 0.002) and between acetate and TNF-α (p = 0.040) as well as FIQ-R scores (p = 0.028), while significantly positive correlations were observed between Kyn/Trp and IL-17 (p = 0.027) as well as IFN-γ (p = 0.003). Conclusions: Our preliminary data suggest that the vitamin D status along with altered gut microbiota metabolism plays a major role in FM-related inflammatory pain. Replication of these findings in a larger cohort is required to provide additional insights. [ABSTRACT FROM AUTHOR] more...
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- 2025
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6. JMJD3 deficiency disturbs dopamine biosynthesis in midbrain and aggravates chronic inflammatory pain.
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He, Xi-Biao, Guo, Fang, Zhang, Wei, Fan, Jiacheng, Le, Weidong, Chen, Qi, Ma, Yongjun, Zheng, Yong, Lee, Sang-Hun, Wang, Hui-Jing, Wu, Yi, Zhou, Qinming, and Yang, Rui
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MEDICAL sciences , *NEUROSCIENCES , *GENETIC transcription regulation , *KNOCKOUT mice , *CHRONIC pain - Abstract
Midbrain dopamine (mDA) neurons participate in a wide range of brain functions through an intricate regulation of DA biosynthesis. The epigenetic factors and mechanisms in this process are not well understood. Here we report that histone demethylase JMJD3 is a critical regulator for DA biosynthesis in adult mouse mDA neurons. Mice carrying Jmjd3 conditional knockout or undergoing pharmaceutical inhibition of JMJD3 showed consistent reduction of DA content in midbrain and striatum. Histological examination of both mice confirmed that TH and NURR1, two key molecules in DA biosynthesis pathway, were decreased in mDA neurons. Mechanistic experiments in vivo and in vitro further demonstrated that the transcriptions of Th and Nurr1 in mDA neurons were suppressed by JMJD3 deficiency, because of increased repressive H3K27me3 and attenuated bindings of JMJD3 and NURR1 on the promoters of both genes. On behavioral level, a significant prolonged inflammation-induced mechanical hyperalgesia was found in conditional knockout mice regardless of sex and age, whereas motor function appeared to be intact. Our findings establish a novel link between DA level in mDA neurons with intrinsic JMJD3 activity, and suggest prolonged chronic inflammatory pain as a major loss-of-function consequence. [ABSTRACT FROM AUTHOR] more...
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- 2024
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7. Trifluoro-Icaritin Ameliorates Neuroinflammation Against Complete Freund's Adjuvant-Induced Microglial Activation by Improving CB2 Receptor-Mediated IL-10/β-endorphin Signaling in the Spinal Cord of Rats.
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Liu, Guangsen, Jia, Dandan, Li, Weiwei, Huang, Zhihua, Shan, Reai, and Huang, Cheng
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The underlying pathogenesis of chronic inflammatory pain is greatly complex, but the relevant therapies are still unavailable. Development of effective candidates for chronic inflammatory pain is highly urgent. We previously identified that trifluoro-icaritin (ICTF) exhibited a significant therapeutic activity against complete Freund's adjuvant (CFA)-induced chronic inflammatory pain, however, the precise mechanisms remain elusive. Here, the paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and CatWalk gait analysis were used to determine the pain-related behaviors. The expression and co-localization of pain-related signaling molecules were detected by Western blot and immunofluorescence staining. Our results demonstrated that ICTF (3.0 mg/kg, i.p.) effectively attenuated mechanical allodynia, thermal hyperalgesia and improved motor dysfunction induced by CFA, and the molecular docking displayed that CB2 receptor may be the therapeutic target of ICTF. Furthermore, ICTF not only up-regulated the levels of CB2 receptor, IL-10, β-endorphin and CD206, but also reduced the expression of P2Y12 receptor, NLRP3, ASC, Caspase-1, IL-1β, CD11b, and iNOS in the spinal cord of CFA rats. Additionally, the immunofluorescence staining from the spinal cord showed that ICTF significantly increased the co-expression between the microglial marker Iba-1 and CB2 receptor, IL-10, β-endorphin, respectively, but markedly decreased the co-localization between Iba-1 and P2Y12 receptor. Conversely, intrathecal administration of CB2 receptor antagonist AM630 dramatically reversed the inhibitory effects of ICTF on CFA-induced chronic inflammatory pain, leading to a promotion of pain hypersensitivity, abnormal gait parameters, microglial activation, and up-regulation of P2Y12 receptor and NLRP3 inflammasome, as well as the inhibition of CB2 receptor and IL-10/β-endorphin cascade. Taken together, these findings highlighted that ICTF alleviated CFA-induced neuroinflammation by enhancing CB2 receptor-mediated IL-10/β-endorphin signaling and suppressing microglial activation in the spinal cord, and uncovered that CB2 receptor may be exploited as a novel and promising target for ICTF treatment of chronic inflammatory pain. [ABSTRACT FROM AUTHOR] more...
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- 2024
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8. The Receptor for Advanced Glycation End-products in the Mouse Anterior Cingulate Cortex is Involved in Neuron‒Astrocyte Coupling in Chronic Inflammatory Pain and Anxiety Comorbidity
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Jiang, Wei, Gong, Minmin, Shen, Linlin, Yu, Chenghui, Ruan, Huaizhen, Chen, Penghui, Gao, Shihao, and Xiao, Zhi
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- 2025
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9. Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients.
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Niu, Zheng, Qu, Shu-Ting, Zhang, Ling, Dai, Jia-Hao, Wang, Ke, Liu, Yun, Chen, Long, Song, Yu, Sun, Ren, Xu, Zhen-Hua, and Zhang, Hai-Long
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CHRONIC pain , *LABORATORY rats , *DORSAL root ganglia , *OSTEOARTHRITIS , *KNEE osteoarthritis , *UBIQUITINATION - Abstract
• Trim14 overexpression in serum from patients with knee osteoarthritis. • Trim14 was highly expressed in the L3-5 DRG and SDH of CFA rats. • Trim14 was mainly expressed in CGRP and IB4 neurons but not glial cells. • Trim14 knockdown increased IκBα expression and inhibited NF-κB phosphorylation. • Trim14 knockdown relieved chronic inflammatory pain and anxiety in CFA rats. Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain. [ABSTRACT FROM AUTHOR] more...
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- 2024
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10. Role of Vitamin D Status and Alterations in Gut Microbiota Metabolism in Fibromyalgia-Associated Chronic Inflammatory Pain
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Caterina Saija, Maria Paola Bertuccio, Alberto Scoglio, Vincenzo Macaione, Francesco Cacciola, Giuseppe Micalizzi, Daniela Caccamo, Carolina Muscoli, and Monica Currò
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fibromyalgia ,chronic inflammatory pain ,gut dysbiosis ,gut microbiota metabolites ,vitamin D ,pro-inflammatory cytokines ,Biology (General) ,QH301-705.5 - Abstract
Background/Objectives: Several studies suggest gut microbiota metabolites as important immuno-modulators in inflammatory pain. We aimed to investigate the relationship between vitamin D status and gut dysbiosis markers in fibromyalgia (FM)-associated chronic inflammation. Methods: Blood samples were collected from sixty-eight female FM patients (49.9 ± 12.35 years). Pain intensity was assessed by FIQ-R. The serum levels of the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-17, IFN-γ, as well as those of vitamin D (25(OH)D3) and the kynurenine/tryptophan ratio (Kyn/Trp) were determined by ELISA and HPLC, respectively. The plasma levels of the SCFAs acetate, butyrate, and propionate were detected by GC-MS. Results: A mean FIQ-R score indicated that the patients could be classified as having moderate FM. The mean levels of all cytokines, but IL-6 and IL-1β, were higher than the normal reference values. The highest concentrations of cytokines were observed in patients showing the highest FIQ-R scores and the lowest 25(OH)D3 levels. Deficient levels of acetate were found paralleled by an increase in Kyn/Trp. The highest acetate concentrations were detected in patients with the lowest FIQ-R scores and 25(OH)D3 levels. Significantly negative correlations were found between 25(OH)D3 concentrations and FIQ-R scores (p = 0.007) as well as IL-17 levels (p = 0.002) and between acetate and TNF-α (p = 0.040) as well as FIQ-R scores (p = 0.028), while significantly positive correlations were observed between Kyn/Trp and IL-17 (p = 0.027) as well as IFN-γ (p = 0.003). Conclusions: Our preliminary data suggest that the vitamin D status along with altered gut microbiota metabolism plays a major role in FM-related inflammatory pain. Replication of these findings in a larger cohort is required to provide additional insights. more...
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- 2025
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11. A neural circuit associated with anxiety‐like behaviors induced by chronic inflammatory pain and the anxiolytic effects of electroacupuncture.
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Wu, Zemin, Shen, Zui, Xu, Yingling, Chen, Shaozong, Xiao, Siqi, Ye, Jiayu, Zhang, Haiyan, Ma, Xinyi, Zhu, Yichen, Zhu, Xixiao, Jiang, Yongliang, Fang, Junfan, Liu, Boyi, He, Xiaofen, Gao, Shuzhong, Shao, Xiaomei, Liu, Jinggen, and Fang, Jianqiao more...
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NEURAL circuitry , *ANXIETY , *CHRONIC pain , *ELECTROACUPUNCTURE , *GABAERGIC neurons , *EXPERIMENTAL arthritis - Abstract
Aims: Negative emotions induced by chronic pain are a serious clinical problem. Electroacupuncture (EA) is a clinically proven safe and effective method to manage pain‐related negative emotions. However, the circuit mechanisms underlying the effect of EA treatment on negative emotions remain unclear. Methods: Plantar injection of complete Freund's adjuvant (CFA) was performed to establish a rat model of chronic inflammatory pain‐induced anxiety‐like behaviors. Adeno‐associated virus (AAV) tracing was used to identify excitatory synaptic transmission from the rostral anterior cingulate cortex (rACC) to the dorsal raphe nucleus (DRN). Employing chemogenetic approaches, we examined the role of the rACC‐DRN circuit in chronic pain‐induced anxiety‐like behaviors and investigated whether EA could reverse chronic pain‐induced dysfunctions of the rACC‐DRN circuit and anxiety‐like behaviors. Results: We found that chemogenetic activation of the rACC‐DRN circuit alleviated CFA‐induced anxiety‐like behaviors, while chemogenetic inhibition of the rACC‐DRN circuit resulted in short‐term CFA‐induced anxiety‐like behaviors. Further research revealed that the development of CFA‐induced anxiety‐like behaviors was attributed to the dysfunction of rACC CaMKII neurons projecting to DRN serotonergic neurons (rACCCaMKII‐DRN5‐HT neurons) but not rACC CaMKII neurons projecting to DRN GABAergic neurons (rACCCaMKII‐DRNGABA neurons). This is supported by the findings that chemogenetic activation of the rACCCaMKII‐DRN5‐HT circuit alleviates anxiety‐like behaviors in rats with chronic pain, whereas neither chemogenetic inhibition nor chemogenetic activation of the rACCCaMKII‐DRNGABA circuit altered CFA chronic pain‐evoked anxiety‐like behaviors in rats. More importantly, we found that EA could reverse chronic pain‐induced changes in the activity of rACC CaMKII neurons and DRN 5‐HTergic neurons and that chemogenetic inhibition of the rACCCaMKII‐DRN5‐HT circuit blocked the therapeutic effects of EA on chronic pain‐induced anxiety‐like behaviors. Conclusions: Our data suggest that the reversal of rACCCaMKII‐DRN5‐HT circuit dysfunction may be a mechanism underlying the therapeutic effect of EA on chronic pain‐induced anxiety‐like behaviors. [ABSTRACT FROM AUTHOR] more...
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- 2024
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12. Efficacy and Safety of Loxoprofen Sodium Hydrogel Patch in Patients with Chronic Inflammatory Pain: A 4-Week Real-World Study
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Chen Y, Bian X, Wang J, Yan F, Gao J, and Sun T
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loxoprofen sodium hydrogel patch ,real-world study ,chronic inflammatory pain ,non-steroidal anti-inflammatory drugs ,Medicine (General) ,R5-920 - Abstract
Yang Chen, Xiaoen Bian, Junnan Wang, Fang Yan, Jing Gao, Tao Sun Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Tao Sun, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, People’s Republic of China, Email suntaosdph@163.comPurpose: Chronic inflammatory pain is usually treated with oral non-steroidal anti-inflammatory drugs (NSAIDs). However, oral NSAIDs can cause some adverse events, and local preparation is an important alternative drug. Currently, small sample clinical studies show that loxoprofen sodium hydrogel patch (LX-P) has good analgesic and anti-inflammatory effects; however, there is a lack of real-world clinical research data.Patients and Methods: This study included 60 patients with chronic inflammatory pain. They were treated with LX-P without affecting their real-world treatment for two weeks.Results: After 2 weeks of continuous medication, 93.33% of the patients stated that the treatment was effective. Only 3.33% of the patients had a relapse after 4 weeks. Moreover, the swelling range and degree of swelling decreased markedly and the dysfunction of the pain site was markedly alleviated. The total satisfaction of patients after treatment reached 90.00%.Conclusion: In this real-world observational study, LX-P showed good efficacy and safety in patients with chronic inflammatory pain.Keywords: loxoprofen sodium hydrogel patch, real-world study, chronic inflammatory pain, non-steroidal anti-inflammatory drugs more...
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- 2024
13. Electroacupuncture promotes synaptic plasticity in rats with chronic inflammatory pain–related depression by upregulating BDNF/TrkB/CREB signaling pathway.
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Yang, Pu, Chen, Haiyan, Wang, Tian, Su, Hong, Li, Jing, He, Yujun, and Su, Shengyong
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NEUROPLASTICITY , *ELECTROACUPUNCTURE , *GABA receptors , *CELLULAR signal transduction , *BRAIN-derived neurotrophic factor , *ENZYME-linked immunosorbent assay , *HIPPOCAMPUS (Brain) - Abstract
Background: Chronic inflammatory pain (CIP) frequently coincides with depression among patients. The onset and development of pain and depression are associated with altered neural synaptic plasticity. Electroacupuncture (EA) can effectively relieve CIP and depression. However, the underlying mechanisms have not been fully illustrated. Objective: To explore whether EA can relieve CIP and depression by regulating hippocampal synaptic plasticity, and the present study offers foundational evidence for the efficacy of EA in treating CIP‐related depression (CIPD). Methods: Rats were divided into four groups: 0.9% normal saline group, complete Freund's adjuvant (CFA) group, CFA + duloxetine group, and CFA + EA group. Pain hypersensitivity was detected by mechanical withdrawal threshold and thermal paw withdrawal latency, and the depression level was gauged using the open field test, the sucrose preference test, and the forced swimming test. The morphology of the hippocampal neurons was observed using Nissl staining. The protein expression levels of synuclein (Syn), postsynaptic density protein‐95 (PSD‐95), brain‐derived neurotrophic factors (BDNFs), tyrosine‐protein kinase B (TrKB), p‐TrkB, cAMP response element binding protein (CREB), and p‐CREB were measured by western blotting and immunofluorescence staining. BDNF and TrkB mRNA expression were detected using quantitative real‐time polymerase chain reaction (PCR) (qRT‐PCR). The content of 5‐hydroxytryptamine (5‐HT) and γ‐aminobutyric acid (GABA) was detected using enzyme‐linked immunosorbent assay, and the glutamic acid (Glu) content was determined using the ultraviolet colorimetry method. The hippocampal neuron ultrastructure was observed using transmission electron microscopy. Results: EA could alleviate CIP and related depressive behaviors as well as protect the hippocampal neuronal structure from damage and regulate 5‐HT/GABA/Glu levels in the hippocampus. Additionally, EA could significantly increase the expression of synapse‐associated proteins such as PSD‐95 and Syn by activating the BDNF/TrKB/CREB signaling pathway. Conclusion: EA improves pain and depressive behaviors in CIPD rats, and the mechanism may be related to synaptic plasticity mediated by the BDNF/TrKB/CREB signaling pathway. [ABSTRACT FROM AUTHOR] more...
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- 2023
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14. Dexamethasone-Loaded biodegradable magnetic microparticles for treatment of CFA-induced chronic pain in rats
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Jin Xin, Zheng Jichun, and Sun Yonghai
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chronic inflammatory pain ,plga microparticles ,dexamethasone ,drug release ,biocompatibility ,magnetic therapy ,local injection ,Polymers and polymer manufacture ,TP1080-1185 - Abstract
Traditional drug solutions or suspensions, have been shown to treat pain in complete Freund’s adjuvant (CFA)-induced chronic inflammatory pain in rats, with or without combination with magnetic therapy. In this study, we aimed to prepare, characterize, and evaluate the therapeutic effects of microparticles containing dexamethasone for local administration and treatment of chronic inflammatory pain. The results showed the following; a) Preparation and characterization: two ratios of poly(lactic-co-glycolic acid) (PLGA)/poly(lactic acid) (PLA) were used. The prepared batches were similar in size and magnetic responsiveness. The microparticle size distribution assessed via electron microscopy suggested a homogeneous distribution and absence of aggregates. Dexamethasone release profiles (microparticles synthesized with a feed ratio of 1:4) showed a sustained release in vitro and good biocompatibility with tissues. b) Therapeutic effect: the treatment effect of dexamethasone-PLGA magnetic microspheres + magnetic therapy was substantially better than that observed for other groups on day 4, as monitored by appearance, mechanical pain threshold, and histological analysis. This type of carrier could be a suitable magnetically retainable local drug delivery system for treating chronic pain. more...
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- 2022
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15. TRPV1 and GABAB1 in the Cerebrospinal Fluid-Contacting Nucleus are Jointly Involved in Chronic Inflammatory Pain in Rats
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Xu LL, Yan Y, Yuan YM, Li Y, Jiang J, and Zhang LC
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cerebrospinal fluid-contacting nucleus ,trpv1 receptor ,gabab1 receptor ,chronic inflammatory pain ,Medicine (General) ,R5-920 - Abstract
Ling-Ling Xu,1– 4,* Yao Yan,1– 3,* Yu-Min Yuan,1– 3 Ying Li,1– 3 Jun Jiang,1– 3 Li-Cai Zhang1– 3 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, People’s Republic of China; 4Department of Anesthesiology, Nanjing Gaochun People’s Hospital, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Cai Zhang, Email licaizhang001@163.comObjective: To assess the receptors of TRPV1 and GABAB1 receptors that were colocalized in cerebrospinal fluid contacting nucleus (CSF-contact nucleus) of chronic inflammatory pain (CIP) rats bringing inspiration for reducing chronic pain.Methods: A rat model of CIP was constructed by plantar injection of complete Freund’s adjuvant (CFA), and the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured 1, 3, 5, 7, 10, and 14 days after plantar injection. In the first part of the experiment, rats with CIP were divided into the immunofluorescence group and the coimmunoprecipitation (Co-IP) group (n = 6). Rats in the immunofluorescence group were injected with the retrograde tracer CB conjugated with Alexa Fluor 594 into the lateral ventricle two days before the injection of CFA into the plantar surface of the left paw. Three days later, rats that exhibited hyperalgesia were perfused, and their brains were extracted and used for double immunofluorescence staining of the CSF-contacting nucleus. Rats in the Co-IP group were anesthetized and dissected 3 days after CFA injection, and fresh brain segments containing the CSF-contacting nucleus were collected for Co-IP to assess the colocalization of TRPV1 and GABAB1 in the CSF-contacting nucleus (n = 6). In the second part of the experiment, SD rats were divided into the normal saline group (control group) and the CFA group. Fresh CSF-contacting nucleus-containing tissues were collected for Western blot analysis 3 days after plantar injection to observe the changes in TRPV1 and GABAB1 expression in the CSF-contacting nucleus.Results: TRPV1 and GABAB1 were co-expressed in the CSF-contacting nucleus in rats with CIP, and their expression was upregulated.Conclusion: TRPV1 and GABAB1 in the CSF-contacting nucleus are jointly involved in CIP in rats, and there is a direct or indirect link between TRPV1 and GABAB1.Keywords: cerebrospinal fluid-contacting nucleus, TRPV1 receptor, GABAB1 receptor, chronic inflammatory pain more...
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- 2022
16. Analgesic effects of saikosaponin A in a rat model of chronic inflammatory pain.
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Lobina, Carla, Lee, Jung Hwan, Pel, Pisey, Chin, Young-Won, Kwon, Hak Cheol, and Colombo, Giancarlo
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CHRONIC pain ,ANIMAL disease models ,SALICYLIC acid ,BUPLEURUM ,HYPERALGESIA ,EXPERIMENTAL arthritis - Abstract
Saikosaponin A (SSA) is the main active ingredient of roots of the East Asian medicinal plant, Bupleurum falcatum L. The present study was aimed at delving into the analgesic properties of SSA in a model of chronic inflammatory pain. To this end, rats were initially treated intraplantarly with complete Freund's adjuvant for induction of hyperalgesia. Twenty-four hours later, rats were acutely treated with SSA (0, 1 and 2 mg/kg, i.p.) and exposed to the Von Frey monofilament test or Randall–Selitto paw pressure test for assessment of mechanical hyperalgesia. Treatment with 2 mg/kg SSA had analgesic effects: the nocifensive reaction (paw withdrawal) occurred later and required application of the nociceptive stimulus at a stronger pressure. The analgesic effects of SSA were of magnitude comparable to that of the effects exerted by the reference compound, acetyl salicylic acid (100 mg/kg, i.p.). The well-described anti-inflammatory properties of SSA likely underlie its analgesic effects. [ABSTRACT FROM AUTHOR] more...
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- 2023
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17. Transcriptional profiles of TGF-β superfamily members in the lumbar DRGs and the effects of activins A and C on inflammatory pain in rats.
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Zhang, Feng-Ming, Wang, Bing, Hu, Han, Zhang, Ying-Ying, Chen, Hao-Hao, Jiang, Zuo-Jie, Zeng, Mei-Xing, and Liu, Xing-Jun
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Signaling by the transforming growth factor (TGF)-β superfamily is necessary for proper neural development and is involved in pain processing under both physiological and pathological conditions. Sensory neurons that reside in the dorsal root ganglia (DRGs) initially begin to perceive noxious signaling from their innervating peripheral target tissues and further convey pain signaling to the central nervous system. However, the transcriptional profile of the TGF-β superfamily members in DRGs during chronic inflammatory pain remains elusive. We developed a custom microarray to screen for transcriptional changes in members of the TGF-β superfamily in lumbar DRGs of rats with chronic inflammatory pain and found that the transcription of the TGF-β superfamily members tends to be downregulated. Among them, signaling of the activin/inhibin and bone morphogenetic protein/growth and differentiation factor (BMP/GDF) families dramatically decreased. In addition, peripherally pre-local administration of activins A and C worsened formalin-induced acute inflammatory pain, whereas activin C, but not activin A, improved formalin-induced persistent inflammatory pain by inhibiting the activation of astrocytes. This is the first report of the TGF-β superfamily transcriptional profiles in lumbar DRGs under chronic inflammatory pain conditions, in which transcriptional changes in cytokines or pathway components were found to contribute to, or be involved in, inflammatory pain processing. Our data will provide more targets for pain research. [ABSTRACT FROM AUTHOR] more...
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- 2023
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18. 基于 TLR4/NF-κB/IL-1β 通路研究人参皂苷 Rg3 对缓解慢性炎症痛的作用机制.
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孙 旭, 朱海丽, 谢 敏, and 高 卉
- Abstract
Objective To study the effect and mechanism of ginsenoside Rg3 on chronic inflammatory pain. Methods The mouse models of chronic inflammatory pain were established by injecting complete Freund's adjuvant into the sole of the foot, and ginsenoside Rg3 was injected intrathecally for spinal cord administration. The mice were randomly divided into the control group, the model group and the ginsenoside Rg3 group, 10 mice in each group. After three days of continuous administration, the changes of foot swelling, pain behavior and physical ability of the mice were observed. The expression of protein in spinal cord tissue of the mice in each group was detected by western blotting. Results After complete Freund's adjuvant intervention, all indexes of the mice changed in different degrees. The expression levels of astrocyte markers in spinal cord tissue: glial fibrillary acidic protein (GFAP), interleukin-1β (IL-1β), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-κB) all increased. Intrathecal administration of ginsenoside Rg3 reduced the number of spontaneous foot contraction in mice, increased the threshold of mechanical pain, increased the stay time and movement distance of rotating rod, and inhibited the expression levels of GFAP, IL-1β, TLR4, MyD88 and NF-κB protein. Conclusion Ginsenoside Rg3 can relieve chronic inflammatory pain by reducing the inflammatory signal of TLR4/NF-κB/IL-1β. [ABSTRACT FROM AUTHOR] more...
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- 2023
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19. CircRNA expression profiling of the rat thalamus in temporomandibular joint chronic inflammatory pain.
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Deng, Haixia, Zhou, Pan, Wang, Jing, Zeng, Jie, and Yu, Cong
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REVERSE transcriptase polymerase chain reaction , *LABORATORY rats , *OROFACIAL pain , *CIRCULAR RNA , *TEMPOROMANDIBULAR joint - Abstract
• 425 circRNAs were identified as significantly differentially expressed in thalamus. • Thalamus may be involved in regulating chronic inflammatory pain in TMJOA. • CircRNA has the potential to be a targeted marker for COFP. Orofacial pain (OFP) induced by temporomandibular disorders (TMDs) is prevalent, affecting approximately 4.6 % of the population. One specific type of TMD is temporomandibular osteoarthritis (TMJOA), a common degenerative disease that significantly impacts patients' quality of life. Differentially expressed circular RNAs (DEcircRNAs) in the thalamus, which serves as a relay station in the orofacial pain transmission pathway, may play a crucial role and serve as potential target markers for inflammation and the progression of inflammatory pain in TMJOA. The aim of this study was to investigate the expression profile of circRNAs in the thalamus of TMJOA. We obtained the circRNA expression profile from the thalamus of a rat model of TMJOA through high-throughput sequencing (HT-seq) and further validated their expression using reverse transcription real-time polymerase chain reaction (RT-qPCR), followed by bioinformatics analysis of the expression data. A total of 425 circRNAs (DESeq2 p- value < 0.05, |log2FoldChange| > 0.0) were identified as significantly differentially expressed by RNA-Seq, comprising 188 up-regulated and 237 down-regulated circRNAs. After validation via RT-qPCR, we employed miRanda software to predict the binding sites of miRNAs for the identified circRNAs to further explore the functions of DEcircRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that DEcircRNAs were primarily enriched in pathways and functions related to synapse development, protein signaling and modification, 'Circadian entertainment', the 'MAPK signaling pathway', and 'Glutamatergic synapse'. These findings suggest that DEcircRNAs in the thalamus play a significant role in the progression of TMJOA and may serve as promising candidate molecular targets for gene therapy. [ABSTRACT FROM AUTHOR] more...
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- 2025
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20. Acupuncture points injection mitigates chronic pain through transient receptor potential V1 in mice
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Hsien-Yin Liao, Ming-Chia Lin, and Yi-Wen Lin
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acupuncture points injection ,chronic inflammatory pain ,dorsal root ganglion ,iba1 ,somatosensory cortex trpv1 ,Medicine - Abstract
Objective(s): Tissue injury in peripheral sites can result in long-term potentiation in nociceptive neurons and surrounding glial cells, potentially resulting in the development of chronic inflammatory pain (CIP). Acupoint injection (AI) is similar to Western phototherapy, which injects solutions at specific sites to mitigate chronic pain. AI has shown greater benefits compared with acupuncture. In this study, we examined the therapeutic effect and explored the underlying mechanisms of AI in mice CIP model. Materials and Methods: We injected thrice complete Freund’s adjuvant (CFA) into the mouse’s hind paw to induce CIP. Results: We found that, after two weeks, CFA injection significantly induced mechanical and thermal hyperalgesia which were attenuated by AI treatment. Transient receptor potential V1 (TRPV1) channels and associated molecules were all increased in CIP in mice dorsal root ganglion (DRG), spinal cord (SC), thalamus, and somatosensory cortex (SSC). The aforementioned molecules were mitigated in AI and Trpv1 knockout mice. Furthermore, Iba1-positive cells (microglial marker) were also potentiated and shared a similar tendency with TRPV1.Conclusion: These findings suggest that AI can alleviate chronic pain by reducing TRPV1 overexpression in both neuronal and microglial cells. Our results suggest new potential therapeutic targets for AI in chronic pain. more...
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- 2022
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21. LncRNA MEG3-TRPV1 signaling regulates chronic inflammatory pain in rats.
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Peng, Jing-Wei, Gu, Yin-Yin, Wei, Jia, Sun, Ye, Zhu, Chun-Long, Zhang, Ling, Song, Yu, Chen, Long, Chen, Xia, Wang, Qian, and Zhang, Hai-Long
- Subjects
- *
CHRONIC pain , *EXPERIMENTAL arthritis , *LINCRNA , *MIDDLE-aged persons , *INTRATHECAL injections , *OSTEOARTHRITIS , *GENE expression - Abstract
Osteoarthritis (OA) is a common osteoarthropathy with chronic inflammatory pain as the core symptom in middle-aged and elderly people. LncRNA MEG3 (Maternally expressed gene 3) is involved in the development of OA via regulation of angiogenesis, which causes the activation and overexpression of transient receptor potential vanilloid type-1 (TRPV1). In this study, we investigated the mechanism of MEG3-TRPV1 signaling in chronic inflammatory pain (CIP) of rat model. Chronic inflammatory pain was modeled using subcutaneous microinjection of complete Freund's adjuvant (CFA) into the left hind paw of rats. We showed that TRPV1 mRNA and protein were significantly increased, while MEG3 mRNA was significantly decreased, in the DRG and SDH of CFA-induced rats. In addition, intrathecal injection of MEG3-overexpressing lentivirus significantly downregulated TRPV1 expression and alleviated chronic inflammatory pain in CFA-induced rats. Treatment with a TRPV1 antagonist also significantly relieved chronic inflammatory pain in CFA-induced rats. In general, our results reveal that MEG3 alleviates chronic inflammatory pain by downregulating TRPV1 expression. These findings may provide new therapeutic targets in the treatment of patients with OA. [ABSTRACT FROM AUTHOR] more...
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- 2022
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22. Dexamethasone-Loaded biodegradable magnetic microparticles for treatment of CFA-induced chronic pain in rats.
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Xin, Jin, Jichun, Zheng, and Yonghai, Sun
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CHRONIC pain ,MAGNETOTHERAPY ,DRUG delivery systems ,TRANSCRANIAL magnetic stimulation ,LACTIC acid ,TREATMENT effectiveness ,PAIN threshold - Abstract
Traditional drug solutions or suspensions, have been shown to treat pain in complete Freund's adjuvant (CFA)-induced chronic inflammatory pain in rats, with or without combination with magnetic therapy. In this study, we aimed to prepare, characterize, and evaluate the therapeutic effects of microparticles containing dexamethasone for local administration and treatment of chronic inflammatory pain. The results showed the following; a) Preparation and characterization: two ratios of poly(lactic-co-glycolic acid) (PLGA)/poly(lactic acid) (PLA) were used. The prepared batches were similar in size and magnetic responsiveness. The microparticle size distribution assessed via electron microscopy suggested a homogeneous distribution and absence of aggregates. Dexamethasone release profiles (microparticles synthesized with a feed ratio of 1:4) showed a sustained release in vitro and good biocompatibility with tissues. b) Therapeutic effect: the treatment effect of dexamethasone-PLGA magnetic microspheres + magnetic therapy was substantially better than that observed for other groups on day 4, as monitored by appearance, mechanical pain threshold, and histological analysis. This type of carrier could be a suitable magnetically retainable local drug delivery system for treating chronic pain. [ABSTRACT FROM AUTHOR] more...
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- 2022
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23. La douleur chronique inflammatoire chez le chien et le chat : état des connaissances, recommandations et développements.
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Marotto, Stéphanie and Verwaerde, Patrick
- Abstract
Copyright of Nouveau Praticien Vétérinaire Canine & Féline is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2022
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24. TRPV1 and GABAB1 in the Cerebrospinal Fluid-Contacting Nucleus are Jointly Involved in Chronic Inflammatory Pain in Rats.
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Xu, Ling-Ling, Yan, Yao, Yuan, Yu-Min, Li, Ying, Jiang, Jun, and Zhang, Li-Cai
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TRPV cation channels ,CHRONIC pain ,SUBSTANCE P receptors ,EXPERIMENTAL arthritis ,RATS ,TRP channels ,VISCERAL pain - Published
- 2022
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25. New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.
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Pangeni R, Poudel S, Herz SM, Berkbigler G, Duerfeldt AS, Damaj MI, and Xu Q
- Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy. To address these limitations, an optimized oil-in-water (o/w) microemulsion formulation was developed using Box-Behnken design to enhance the solubility and intestinal permeability of A190. The A190 microemulsion exhibited physical stability with a droplet size of approximately 100 nm and a drug loading efficiency of greater than 95%. The effective and apparent permeability of A190 from the microemulsion was significantly higher compared to that of free A190 dispersion, respectively. Additionally, no significant impact on the cell viability was observed, indicating less toxicity and a good biocompatibility of the formulation components. The oral bioavailability of A190 microemulsion was approximately 5-fold higher compared to A190 dispersion, demonstrating the microemulsion's potential to greatly enhance the oral bioavailability of hydrophobic drugs. Furthermore, our findings reveal that orally administered A190 microemulsion effectively reduced CIPN-induced mechanical hypersensitivity, likely mediated through PPARα activation. A190 microemulsion was found to be equally effective at reducing the chronic inflammatory complete Freund's adjuvant-induced pain. These results underscore A190s potential as a nonopioid therapeutic candidate, utilizing a novel microemulsion formulation for the management of chemotherapy-induced neuropathic pain and chronic inflammatory pain. more...
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- 2025
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26. Anxiolytic effect of GABAergic neurons in the anterior cingulate cortex in a rat model of chronic inflammatory pain
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Fang-bing Shao, Jun-fan Fang, Si-si Wang, Meng-ting Qiu, Dan-ning Xi, Xiao-ming Jin, Jing-gen Liu, Xiao-mei Shao, Zui Shen, Yi Liang, Jian-qiao Fang, and Jun-ying Du
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Chronic inflammatory pain ,Anxiety-like behavior ,GABAergic system ,Anterior cingulate cortex ,synaptic transmission ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Chronic 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. more...
- Published
- 2021
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27. Anterior Insular-nucleus Accumbens Pathway Controls Refeeding-induced Analgesia under Chronic Inflammatory Pain Condition.
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Lee, Grace J., Kim, Yea Jin, Shim, Sang Wook, Lee, Kihwan, and Oh, Seog Bae
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CHRONIC pain , *INSULAR cortex , *ANALGESIA , *NUCLEUS accumbens , *PAIN management , *NEURAL circuitry , *INGESTION disorders - Abstract
• D2R antagonist reverses refeeding-induced analgesia under chronic pain conditions. • aIC-NAcS circuit is activated in chronic inflammatory pain model. • Refeeding suppresses aIC-NAcS circuit under chronic inflammatory pain condition. • Chemogenetic activation of aIC-NAcS circuit reverses refeeding-induced analgesia. Feeding behaviors are closely associated with chronic pain in adult rodents. Our recent study revealed that 2 h refeeding after 24 h fasting (i.e., refeeding) attenuates pain behavior under chronic inflammatory pain conditions. However, while brain circuits mediating fasting-induced analgesia have been identified, the underlying mechanism of refeeding-induced analgesia is still elusive. Herein, we demonstrate that the neural activities in the nucleus accumbens shell (NAcS) and anterior insular cortex (aIC) were increased in a modified Complete Freund's Adjuvant (CFA)-induced chronic inflammatory pain condition, which was reversed by refeeding. We also found that refeeding reduced the enhanced excitability of aICCaMKII–NAcSD2R projecting neurons in this CFA model. Besides, chemogenetic inhibition of aICCaMKII–NAcSD2R neural circuit suppressed chronic pain behavior while activation of this circuit reversed refeeding-induced analgesia. Thus, the present study suggests that aICCaMKII–NAcSD2R neural circuit mediates refeeding-induced analgesia, thereby serving as a potential therapeutic target to manage chronic pain. [ABSTRACT FROM AUTHOR] more...
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- 2022
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28. Management of Osteoarthritis: Expert Opinion on NSAIDs.
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Magni, Alberto, Agostoni, Piergiuseppe, Bonezzi, Cesare, Massazza, Giuseppe, Menè, Paolo, Savarino, Vincenzo, and Fornasari, Diego
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- *
OSTEOARTHRITIS , *DRUG therapy , *OLDER people , *DRUG interactions , *NONSTEROIDAL anti-inflammatory agents , *PATIENT compliance - Abstract
Osteoarthritis (OA) is a leading cause of disability among older adults worldwide. Treatment aims are to alleviate inflammatory pain and improve physical function through non-pharmacological and pharmacological interventions. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line therapy. However, selection is challenged by patient age, comorbidities and polypharmacy, and by the drug's benefit/risk balance, all of which together influence the risk of cardiovascular (CV), gastrointestinal (GI) and renal adverse events (AEs). While the efficacy profile of the various NSAIDs is delineated, the differences in their safety profile are not straightforward. This narrative review provides practical indications by a multidisciplinary Italian expert panel for general practitioners and specialists managing OA patients with chronic inflammatory pain; the goal is to maximize therapy efficacy while reducing untoward effects caused by inappropriate NSAID use. The discussion on the best approach to NSAIDs spanned the following topics: (1) patient evaluation: investigate pain origin, duration and components together with possible risk factors for CV, GI and renal AEs; (2) non-pharmacological interventions: the physiatrist provides a person-centered, holistic approach accounting for all patient aspects; (3) pharmacological interventions: patient profile and drugs' pharmacological properties affect NSAID selection, which drugs to be used in combination or to be avoided, formulation and therapy duration; (4) the pharmacologist's, general practitioner's and pain therapist's points of view; (5) NSAID safety: the individual baseline risk and the drug's safety profile are major determinants of CV, GI and renal risk; consider possible drug–drug interactions; (6) periodical re-evaluation of treatment response and adherence, using scales to assess pain and function. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
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29. Anxiolytic effect of GABAergic neurons in the anterior cingulate cortex in a rat model of chronic inflammatory pain.
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Shao, Fang-bing, Fang, Jun-fan, Wang, Si-si, Qiu, Meng-ting, Xi, Dan-ning, Jin, Xiao-ming, Liu, Jing-gen, Shao, Xiao-mei, Shen, Zui, Liang, Yi, Fang, Jian-qiao, and Du, Jun-ying
- Subjects
GABAERGIC neurons ,ANIMAL disease models ,GABA agents ,CHRONIC pain ,CINGULATE cortex ,PYRAMIDAL neurons ,NEURAL transmission - Abstract
Chronic 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 GABA
A R agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABAA R 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. [ABSTRACT FROM AUTHOR] more...- Published
- 2021
- Full Text
- View/download PDF
30. Inhibition Of Monocarboxylate Transporter 1 In Spinal Cord Horn Significantly Reverses Chronic Inflammatory Pain
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He J, Yu L, Wang Z, Wang Q, Cao JL, and Gu L
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chronic inflammatory pain ,monocarboxylate transporter 1 ,spinal dorsal horn ,astrocyte ,synaptic plasticity ,Medicine (General) ,R5-920 - Abstract
Jian-hua He,1,* Ling Yu,2,* Zhi-yong Wang,1 Qiang Wang,3 Jun-Li Cao,4 Lian-bing Gu1 1Department of Anesthesiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Ultrasound, Affiliated Hospital of Integrate Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing,People’s Republic of China; 3Department of Anesthesiology, Nanjing Meishan Hospital, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian-bing GuDepartment of Anesthesiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Baiziting 42#, Nanjing, Jiangsu 210009, People’s Republic of ChinaTel/fax +86 25 8328 4765Email lbg6519@163.comPurpose: Chronic inflammatory pain is a common condition in the clinic, and the underlying mechanism is not being completely understood. Various studies have demonstrated that central and peripheral sensitization and synaptic plasticity could play crucial functions in chronic inflammatory pain. Moreover, families of monocarboxylate transporters (MCTs) are closely related to cellular metabolism and synaptic plasticity, and it is also reported that MCTs participate in chronic inflammatory pain. Nevertheless, there is a probability of the engaging role of MCT 1 is in chronic inflammatory pain, but its specific cellular level mechanism is yet to be investigated. In our study, we hypothesized that MCT 1 in the spinal dorsal horn plays an important part in chronic inflammatory pain.Methods: In experiment A, rats were gone through nociceptive behavioral testing at 1 d day before and 1 d, 3 d, and 7 d after completing complete Freund’s adjuvant (CFA) injection. The specimens collected for detecting MCT 1 by Western blotting. In experiment B, rats were randomly divided into four groups. Intrathecal injection of MCT 1 inhibitor and nociceptive behavioral tests were performed 1 d day before and 1 d, 3 d, 7 d, 14 d, and 21 d after CFA injection. MCT 1 and p-ERK levels in spinal dorsal horn were measured by Western blotting, and GFAP in spinal dorsal horn was detected by immunofluorescence.Results: The expression of MCT 1 in the spinal dorsal horn was increased during chronic inflammatory pain in rats. The intrathecal injection of an MCT 1 inhibitor evidently diminished the expression of MCT 1 and GFAP in the spinal dorsal horn, and the behavioral nociceptive responses were also attenuated. Meanwhile, the expression of p-ERK was also decreased by the intrathecal injection of an MCT 1 inhibitor.Conclusion: Our results indicate that MCT 1 very likely play a critical role in regulating chronic inflammatory pain and may influence the regulation of synaptic plasticity via ERK in the spinal dorsal horn of rats.Keywords: chronic inflammatory pain, monocarboxylate transporter 1, spinal dorsal horn, astrocyte, synaptic plasticity more...
- Published
- 2019
31. Epigenetic suppression of liver X receptor β in anterior cingulate cortex by HDAC5 drives CFA-induced chronic inflammatory pain
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Yu-Jiao Li, Kun Zhang, Ting Sun, Jian Wang, Yan-Yan Guo, Le Yang, Qi Yang, Yan-Jiao Li, Shui-Bing Liu, Ming-Gao Zhao, and Yu-Mei Wu
- Subjects
Chronic inflammatory pain ,Anterior cingulate cortex ,Liver X receptors ,Histone modification ,Neuroinflammation ,Neurotransmission ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Liver X receptors (LXRs), including LXRα and LXRβ, are key regulators of transcriptional programs for both cholesterol homeostasis and inflammation in the brain. Here, the modes of action of LXRs and the epigenetic mechanisms regulating LXRβ expression in anterior cingulate cortex (ACC) of chronic inflammatory pain (CIP) are investigated. Methods The deficit of LXR isoform and analgesic effect of LXR activation by GW3965 were evaluated using the mouse model of CIP induced by hindpaw injection of complete Freund’s adjuvant (CFA). The mechanisms involved in GW-mediated analgesic effects were analyzed with immunohistochemical methods, ELISA, co-immunoprecipitation (Co-IP), Western blot, and electrophysiological recording. The epigenetic regulation of LXRβ expression was investigated by chromatin immunoprecipitation, quantitative real-time PCR, and sequencing. Results We revealed that CFA insult led to LXRβ reduction in ACC, which was associated with upregulated expression of histone deacetylase 5 (HDAC5), and knockdown of LXRβ by shRNA led to thermal hyperalgesia. Co-IP showed that LXRβ interacted with NF-κB p65 physically. LXRβ activation by GW3965 exerted analgesic effects by inhibiting the nuclear translocation of NF-κB, reducing the phosphorylation of mitogen-activated protein kinases (MAPKs) in ACC, and decreasing the promoted input-output and enhanced mEPSC frequency in ACC neurons after CFA exposure. In vitro experiments confirmed that HDAC5 triggered histone deacetylation on the promoter region of Lxrβ, resulting in downregulation of Lxrβ transcription. Conclusion These findings highlight an epigenetic mechanism underlying LXRβ deficits linked to CIP, and LXRβ activation may represent a potential novel target for the treatment of CIP with an alteration in inflammation responses and synaptic transmission in ACC. more...
- Published
- 2019
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32. Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex
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Fangbing Shao, Junfan Fang, Mengting Qiu, Sisi Wang, Danning Xi, Xiaomei Shao, Xiaofen He, Jianqiao Fang, and Junying Du
- Subjects
electroacupuncture ,chronic inflammatory pain ,anterior cingulate cortex ,parvalbumin ,anxiety ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Chronic inflammatory pain is a common clinical disease that tends to be associated with negative emotions such as anxiety and depression. The anterior cingulate cortex (ACC) is involved in pain and pain-related anxiety, and γ-aminobutyric acid (GABA)-ergic interneurons play an important role in chronic pain and anxiety. Electroacupuncture (EA) has good analgesic and antianxiety effect, but the underlying mechanisms have not yet been fully elucidated. In this study, we established a chronic inflammatory pain model and observed that this model induced anxiety-like behaviors and decreased the numbers of parvalbumin (PV) and somatostatin (SOM) positive cells. Activation of PV but not SOM interneurons by chemogenetic techniques alleviated anxiety-like behaviors and pain sensation. EA treatment improved pain sensation, anxiety-like behaviors and increased the number of PV- positive cells in the ACC, but did not affect on the number of SOM-positive cells in the ACC. Moreover, specific inhibition of PV interneurons by chemogenetic methods reversed the analgesic and antianxiety effects of EA. These results suggest that EA ameliorates chronic inflammatory pain and pain-related anxiety by upregulating PV but not SOM interneurons in the ACC. more...
- Published
- 2021
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33. Electroacupuncture Inhibits the Interaction between Peripheral TRPV1 and P2X3 in Rats with Different Pathological Pain.
- Author
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Yingjun LIU, Junying DU, Junfan FANG, Xuaner XIANG, Yingling XU, Sisi WANG, Haiju SUN, and Jianqiao FANG
- Subjects
TRPV cation channels ,ELECTROACUPUNCTURE ,DORSAL root ganglia ,NEURALGIA ,NERVOUS system injuries - Abstract
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. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
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34. Electroacupuncture Ameliorates Chronic Inflammatory Pain-Related Anxiety by Activating PV Interneurons in the Anterior Cingulate Cortex.
- Author
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Shao, Fangbing, Fang, Junfan, Qiu, Mengting, Wang, Sisi, Xi, Danning, Shao, Xiaomei, He, Xiaofen, Fang, Jianqiao, and Du, Junying
- Subjects
CINGULATE cortex ,ELECTROACUPUNCTURE ,INTERNEURONS ,EMOTIONS ,CHRONIC pain ,PAIN ,PAIN tolerance - Abstract
Chronic inflammatory pain is a common clinical disease that tends to be associated with negative emotions such as anxiety and depression. The anterior cingulate cortex (ACC) is involved in pain and pain-related anxiety, and γ-aminobutyric acid (GABA)-ergic interneurons play an important role in chronic pain and anxiety. Electroacupuncture (EA) has good analgesic and antianxiety effect, but the underlying mechanisms have not yet been fully elucidated. In this study, we established a chronic inflammatory pain model and observed that this model induced anxiety-like behaviors and decreased the numbers of parvalbumin (PV) and somatostatin (SOM) positive cells. Activation of PV but not SOM interneurons by chemogenetic techniques alleviated anxiety-like behaviors and pain sensation. EA treatment improved pain sensation, anxiety-like behaviors and increased the number of PV- positive cells in the ACC, but did not affect on the number of SOM-positive cells in the ACC. Moreover, specific inhibition of PV interneurons by chemogenetic methods reversed the analgesic and antianxiety effects of EA. These results suggest that EA ameliorates chronic inflammatory pain and pain-related anxiety by upregulating PV but not SOM interneurons in the ACC. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
- Full Text
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35. Blockade of Spinal EphA4 Reduces Chronic Inflammatory Pain in Mice.
- Author
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Wang, Yin, Wen, Chuanyun, Xie, Guozhu, and Jiang, Lin
- Subjects
CHRONIC pain ,CANCER pain ,NEUROPLASTICITY ,NEURALGIA ,INTRATHECAL injections ,LABORATORY mice - Abstract
Background: Erythropoietin-producing hepatocellular (Ephs) receptor and their ligands, ephrins, orchestrate the induction of cell proliferation and migration, axonal guidance, synaptic genesis and synaptic plasticity in the central nervous system. Previous studies demonstrated that EphBs/ephrinBs participate in the pathophysiology of neuropathic pain, inflammatory pain and bone cancer pain, but the role of EphA4 in the regulation of pain in the spinal cord is unknown. Therefore, we explored the role of EphA4 receptor in regulating chronic inflammatory pain. Methods: We established a mouse model of chronic inflammatory pain through plantar injection of complete freund's adjuvant (CFA) and assessed EphA4 expression in spinal cord by western blotting. EphA4 receptor was blocked by intrathecal injection of EphA4-Fc, an EphA4 antagonist, and pain behaviors were measured by assessing thermal hyperalgesia and mechanical allodynia. Finally, immunohistochemistry was performed to analyze the changes in the expression of Fos protein in spinal cord after blocking EphA4 receptor. Results: Plantar injection of CFA produced persistent thermal hyperalgesia and mechanical allodynia, which was accompanied by significant increases in spinal EphA4 and Fos expression. Blocking spinal EphA4 receptor suppressed CFA-induced pain behaviors and reduced the expression of Fos protein in spinal cord. Conclusions: Our study demonstrated that EphA4 receptor is involved in the generation and maintenance of CFA-induced chronic inflammatory pain and that blocking the spinal EphA4 receptor could relieve persistent pain behaviors in mice. [ABSTRACT FROM AUTHOR] more...
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- 2021
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36. Pain aversion and anxiety-like behavior occur at different times during the course of chronic inflammatory pain in rats
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Wu YY, Yao XM, Jiang YL, He XF, Shao XM, Du JY, Shen Z, He QY, and Fang JQ
- Subjects
Pain ,pain aversion ,pain affection ,anxiety-like behavior ,chronic inflammatory pain ,rat ,Medicine (General) ,R5-920 - Abstract
Yuanyuan Wu,1 Xinmiao Yao,2 Yongliang Jiang,1 Xiaofen He,1 Xiaomei Shao,1 Junying Du,1 Zui Shen,1 Qiaoying He,1 Jianqiao Fang1 1Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, China Abstract: Pain is considered a multidimensional conscious experience that includes a sensory component and a negative affective-motivational component. The negative affective-motivational component of pain is different from the sensory component and amplifies the pain experience. Nowadays, a significant number of preclinical research groups have focused their attention on the affective symptoms of pain. In the present study, we investigated the pain aversion and anxiety-like behavior of the complete Freund’s adjuvant (CFA)-induced chronic pain model. CFA rats experienced spontaneous pain during pain-paired conditioning (pain aversion) and spontaneous pain produces an affective response (anxiety-like behavior). Moreover, pain aversion was gradually attenuated, while the anxiety-like behavior increased in 4 weeks. Therefore, although the negative effect (including pain aversion and anxiety) is always associated with hyperalgesia, the manifestations of negative effect may follow different time courses, which may influence the progress of primary disease. The findings illustrate that targeted therapy should focus on a specific aspect in different stages of pain. Our study emphasizes the necessity of using multiple tests to study pain comorbidities. Keywords: pain, pain aversion, pain affection, anxiety-like behavior, chronic inflammatory pain, rat more...
- Published
- 2017
37. 牛蒡皮固体培养灵芝多糖对慢性炎性痛小鼠的 影响.
- Author
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董玉玮, 蒋如梦, 苗敬芝, 李文, 高甜慧, and 胡传银
- Abstract
Copyright of Food Research & Development is the property of Food Research & Development Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2019
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38. Inhibition of spinal Rac1 attenuates chronic inflammatory pain by regulating the activation of astrocytes.
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Wan, Yantong, Zhou, Jieshu, Zhang, Panpan, Lin, Xuemei, and Li, Hao
- Subjects
- *
GLIAL fibrillary acidic protein , *CHRONIC pain , *CENTRAL nervous system injuries , *ASTROCYTES , *GLYCINE receptors , *BOTULINUM A toxins , *BOTULINUM toxin - Abstract
Spinal astrocyte-mediated neuroinflammation is an important mechanism for the maintenance of chronic inflammatory pain. Previous studies have investigated that Ras-related C3 botulinum toxin substrate 1 (Rac1) is closely related to astrocyte activation after central nervous system injury. However, the role of Rac1 in astrocyte activation in chronic inflammatory pain has not been reported. Complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model and LPS-stimulated astrocytes were used to investigate the role of Rac1 in astrocyte activation and the underlying mechanism. Rac1-interfering adeno-associated virus (AAV) targeting astrocytes was delivered to spinal astrocytes by intrathecal administration and a Rac1 specific inhibitor, NSC23766, was used to block cultured astrocytes. The glial fibrillary acidic protein (GFAP), proinflammatory cytokines, p-NF-κB, and nod-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome were detected by RT-qPCR, Western blotting, and immunofluorescence to investigate the activation of astrocytes. CFA induced spinal astrocyte activation and increased the expression of active Rac1 in spinal astrocytes. Knockdown of astrocyte Rac1 alleviated chronic inflammatory pain and inhibited astrocyte activation. Inhibition of Rac1 activation in cultured astrocytes decreased the expression of GFAP and proinflammatory cytokines. Knockdown of Rac1 inhibited the increase of expression of NLRP3 inflammasome and phosphorylation of NF-κB in the spinal lumbar enlargement after CFA injection. Similarly, the inhibition of Rac1 suppressed the increase of NLRP3 inflammasome and p-NF-κB protein level after LPS stimulation. Knockdown of astrocyte Rac1 attenuated CFA-induced hyperalgesia and astrocyte activation possibly by blocking the expression of NLRP3 inflammasome and phosphorylation of NF-κB. • CFA induced spinal astrocyte activation and increased the expression of active Rac1 in spinal astrocytes. • Knockdown of astrocyte Rac1 attenuated CFA-induced hyperalgesia and astrocyte activation. • Rac1 inhibition significantly attenuates astrocyte activation by blocking the expression of NLRP3 inflammasome and p-NF-κB. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
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39. Emodin inhibits HDAC6 mediated NLRP3 signaling and relieves chronic inflammatory pain in mice.
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Cheng, Ding-Wen, Xu, Yiwen, Chen, Tao, Zhen, Shu-Qing, Meng, Wei, Zhu, Hai-Li, Liu, Ling, Xie, Min, and Zhen, Fangshou
- Subjects
- *
EMODIN , *CHRONIC pain , *NLRP3 protein , *IONIC bonds , *HISTONE deacetylase - Abstract
Chronic pain reduces the quality of life and ability to function of individuals suffering from it, making it a common public health problem. Neuroinflammation which is mediated by the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in the spinal cord participates and modulates chronic pain. A chronic inflammatory pain mouse model was created in the current study by intraplantar injection of complete Freund's adjuvant (CFA) into C57BL/6J left foot of mice. Following CFA injection, the mice had enhanced pain sensitivities, decreased motor function, increased spinal inflammation and activated spinal astrocytes. Emodin (10 mg/kg) was administered intraperitoneally into the mice for 3 days. As a result, there were fewer spontaneous flinches, higher mechanical threshold values and greater latency to fall. Additionally, in the spinal cord, emodin administration reduced leukocyte infiltration level, downregulated protein level of IL-1β, lowered histone deacetylase (HDAC)6 and NLRP3 inflammasome activity and suppressed astrocytic activation. Emodin also binds to HDAC6 via four electrovalent bonds. In summary, emodin treatment blocked the HDAC6/NLRP3 inflammasome signaling, suppresses spinal inflammation and alleviates chronic inflammatory pain. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
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40. Effect of electroacupuncture on inflammatory response and immune cells in mice with chronic inflammatory pain.
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Yang JL, Shi JJ, Ma NQ, Jiang MJ, Peng R, Chen LY, Yu ML, and Lu SF
- Subjects
- Mice, Animals, Tumor Necrosis Factor-alpha genetics, NLR Family, Pyrin Domain-Containing 3 Protein, Mice, Inbred C57BL, Interleukin-1beta, Freund's Adjuvant, Electroacupuncture, Chronic Pain genetics, Chronic Pain therapy
- Abstract
Objectives: To observe the effects of electroacupuncture(EA) on local inflammatory mediators and macrophage polarization, and immune cells in the spleen of mice with chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in the hind paw, so as to investigate the immunoinflammatory regulatory mechanisms of EA in relieving pain and swelling in mice with chronic inflammatory pain., Methods: Thirty C57BL/6 mice were randomly divided into control, model, and EA groups, with 10 mice in each group. Chronic inflammatory pain model were established by subcutaneous injection of 20 μL CFA solution in the left hind paw for 7 consecutive days. After modeling, mice in the EA group received EA at bilateral "Zusanli"(ST36) for 20 min (2 Hz/100 Hz, 1 mA) once a day for 18 consecutive days. Mechanical pain threshold, heat pain thresholds, and paw thickness were measured before and after mode-ling, and after interventions. Western blot was used to detect the expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and NOD-like receptor protein 3 (NLRP3) in the paw tissue. Immunohistochemistry was used to detect the positive expression of M1-type macrophage marker inducible nitric oride synthase (iNOS) and M2-type marker CD206 in the paw, and flow cytometry was used to detect the proportion of F4/80
+ CD11b+ macrophages, Ly6G+ CD11b+ neutrophils, and CD25+ Foxp3+ regulatory T cells (Treg) in the spleen., Results: Compared with the control group, mechanical pain and heat pain thresholds were significantly reduced( P <0.000 1), while paw thickness, expressions of IL-1β, TNF-α, and NLRP3 in the paw, and positive expression of M1 macrophage marker iNOS in the paw, the proportions of macrophages and neutrophils in the spleen were significantly increased ( P <0.000 1, P <0.001) in the model group. Compared with the model group, mechanical pain threshold and heat pain thresholds, CD206 positive expression in the paw, and Treg cell proportion in spleen were significantly increased ( P <0.01), while paw thickness, the expressions of IL-1β, TNF-α and NLRP3 in the paw, as well as the positive expression of M1 macrophage marker iNOS in the paw, the proportions of macrophages and neutrophils in the spleen were significantly reduced ( P <0.001, P <0.01, P <0.05)in mice of the EA group after intervention., Conclusions: EA may alleviate pain and swelling in mice with chronic inflammatory pain by regulating the numbers of macrophages, neutrophils, and Treg cells, as well as promoting M2 polarization of local macrophages and inhibiting the release of pro-inflammatory cytokines. more...- Published
- 2024
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41. TRPA1 involvement in analgesia induced by Tabernaemontana catharinensis ethyl acetate fraction in mice.
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Brum, Evelyne da Silva, Becker, Gabriela, Fialho, Maria Fernanda Pessano, Casoti, Rosana, Trevisan, Gabriela, and Oliveira, Sara Marchesan
- Abstract
Background: Ionic channels such as the transient receptor potential ankyrin 1 (TRPA1) are essential for the detection and transmission of painful stimuli. In this sense, new TRPA1 antagonists have been searched as analgesics.Purpose: Preclinical studies support the antinociceptive activity of Tabernaemontana catharinensis ethyl acetate fraction (Eta), which has constituents previously identified as TRPA1 antagonists (gallic acid). It was verified for the first time the involvement of the TRPA1 on Eta's antinociceptive and anti-inflammatory effects in mice pain models.Study Design: It was evaluated the Eta's effect (0.01-100 mg/kg, oral route) on nociceptive (spontaneous nociception, mechanical and cold allodynia) and inflammatory (paw edema) parameters in pain models involved with TRPA1 activation.Methods: Firstly, it was investigated the ability of Eta to act on TRPA1 or TRPV1 channels (Ca2+influx and binding assays in mice spinal cords). Next, it was evaluated the Eta's antinociceptive and anti-inflammatory effects after intraplantar injection of TRPA1 agonists (hydrogen peroxide, cinnamaldehyde or allyl isothiocyanate) in male Swiss mice (30-35 g). Moreover, the Eta's antinociceptive effects were evaluated on complete Freund's adjuvant (CFA)-induced chronic inflammatory pain (CIP), postoperative pain and on paclitaxel-induced peripheral neuropathy (PIPN). Oxidative parameters were evaluated in mice paw utilized for CFA induced-CIP model.Results: Eta inhibited the TRPA1 agonist-induced Ca2+ influx [Imax = 72.4 ± 1.5%; IC50 = 0.023(0.004-0.125)µg/ml], but not TRPV1 agonist-induced, nor was able to displace [3H]-resiniferatoxin (TRPV1 agonist) binding. Eta (0.1-100 mg/kg) inhibited the spontaneous nociception [ID50 = 0.043(0.002-0.723)mg/kg], mechanical [ID50 = 7.417(1.426-38.570)mg/kg] and cold allodynia, and edema development caused by TRPA1 agonists. Moreover, Eta (100 mg/kg) prevented and reversed the CFA-induced CIP (Imax = 55.8 ± 13.7%, Imax = 80.4 ± 5.1%, respectively) and postoperative pain (Imax = 88.0 ± 11.6%, Imax = 51.3 ± 14.9%, respectively), been also effective in reversing the acute (Imax = 94.4 ± 12.4%) and chronic (Imax = 86.8 ± 8.6%) PIPN. These effects seem to occur by TRPA1 channels pathway, and independently of TRPV1 or oxidative mechanisms.Conclusion: Our results demonstrate that Eta-induced antinociception and anti-inflammatory effects occur by TRPA1 inhibition making possible the use of this preparation as a potential therapeutic agent to treat pathological pains. [ABSTRACT FROM AUTHOR] more...- Published
- 2019
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- View/download PDF
42. Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2.
- Author
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Oliveira, Ana M. M., Litke, Christian, Hagenston, Anna M., Bading, Hilmar, Mauceri, Daniela, Paldy, Eszter, Jianning Lu, and Kuner, Rohini
- Abstract
Chronic pain is a pathological manifestation of neuronal plasticity supported by altered gene transcription in spinal cord neurons that results in long-lasting hypersensitivity. Recently, the concept that epigenetic regulators might be important in pathological pain has emerged, but a clear understanding of the molecular players involved in the process is still lacking. In this study, we linked Dnmt3a2, a synaptic activity-regulated de novo DNA methyltransferase, to chronic inflammatory pain.We observed that Dnmt3a2 levels are increased in the spinal cord of adult mice following plantar injection of Complete Freund's Adjuvant, an in vivo model of chronic inflammatory pain. In vivo knockdown of Dnmt3a2 expression in dorsal horn neurons blunted the induction of genes triggered by Complete Freund's Adjuvant injection. Among the genes whose transcription was found to be influenced by Dnmt3a2 expression in the spinal cord is Ptgs2, encoding for Cox-2, a prime mediator of pain processing. Lowering the levels of Dnmt3a2 prevented the establishment of long-lasting inflammatory hypersensitivity. These results identify Dnmt3a2 as an important epigenetic regulator needed for the establishment of central sensitization. Targeting expression or function of Dnmt3a2 may be suitable for the treatment of chronic pain. [ABSTRACT FROM AUTHOR] more...
- Published
- 2019
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43. Celastrol ameliorates inflammatory pain and modulates HMGB1/NF-κB signaling pathway in dorsal root ganglion.
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Zhang, Xiumei, Zhao, Wenpin, Liu, Xingfang, Huang, Zhihua, Shan, Reai, and Huang, Cheng
- Subjects
- *
DORSAL root ganglia , *WESTERN immunoblotting - Abstract
Highlights • Establishing CFA-induced chronic inflammatory pain rat model was to explore the role of neuroinflammation in CFA rats. • Celastrol possessing anti-inflammatory activity was further confirmed in DRG of CFA rats. • Elucidating the molecular mechanism by which celastrol alleviates CFA-induced inflammatory pain in DRG. Abstract Evidences reported that high mobility group box 1 (HMGB1) played a pivotal role in the modulation of chronic inflammatory pain. Celastrol, a bioactive component extracted from Tripterygium wilfordii Hook , possesses anti-inflammatory activity, but the underlying mechanism remains to be fully clarified. We aim to investigate whether HMGB1 in dorsal root ganglion (DRG) participates in the effect of celastrol on inflammatory pain. Complete Freund's adjuvant (CFA)-induced inflammatory pain rat model was used. Paw withdrawal latency (PWL) was detected to evaluate the effects of celastrol on CFA-evoked inflammatory pain. After application of celastrol (1mg/kg, i.p.) on day 1, 3, 7 and 14 post-CFA injection, the expression levels of HMGB1, NF-κB, some proinflammatory markers, GFAP and CD11b in DRG were determined by qRT-PCR and western blot analysis. These results showed that celastrol significantly suppressed HMGB1, NF-κB and IL-1β mRNA and protein expression in DRG and alleviated CFA-evoked thermal hyperalgesia. Furthermore, celastrol obviously inhibited COX-2 protein expression and down-regulated IL-6, IL-17, TNF-α, MCP-1, GFAP and CD11b mRNA levels in DRG of CFA rats. Collectively, the present study firstly provide evidences of the anti-inflammatory effect of celastrol via suppressing CFA-induced the activation of HMGB1/NF-κB signaling pathway in DRG, which maybe a potential therapeutic target for celastrol alleviating inflammatory pain. [ABSTRACT FROM AUTHOR] more...
- Published
- 2019
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44. Analgesic Effect of Methane Rich Saline in a Rat Model of Chronic Inflammatory Pain.
- Author
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Zhou, Shu-Zhuan, Zhou, Ya-Lan, Ji, Feng, Li, Hao-Ling, Lv, Hu, Zhang, Yan, and Xu, Hua
- Subjects
- *
CHRONIC pain treatment , *LABORATORY rats , *OXIDATIVE stress , *REPERFUSION injury ,ANALGESIC effectiveness - Abstract
How oxidative stress contributes to neuro-inflammation and chronic pain is documented, and methane is reported to protect against ischemia-reperfusion injury in the nervous system via anti-inflammatory and antioxidant properties. We studied whether methane in the form of methane rich saline (MS) has analgesic effects in a monoarthritis (MA) rat model of chronic inflammatory pain. Single and repeated injections of MS (i.p.) reduced MA-induced mechanical allodynia and multiple methane treatments blocked activation of glial cells, decreased IL-1β and TNF-α production and MMP-2 activity, and upregulated IL-10 expression in the spinal cord on day 10 post-MA. Furthermore, MS reduced infiltrating T cells and expression of IFN-γ and suppressed MA-induced oxidative stress (MDA and 8-OHDG), and increased superoxide dismutase and catalase activity. Thus, MS may offer anti-inflammatory and antioxidant effects to reduce chronic inflammatory pain. [ABSTRACT FROM AUTHOR] more...
- Published
- 2018
- Full Text
- View/download PDF
45. Cholinergic neurons in medial septum maintain anxiety-like behaviors induced by chronic inflammatory pain.
- Author
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Jiang, Ying-Ying, Zhang, Yu, Cui, Shuang, Liu, Feng-Yu, Yi, Ming, and Wan, You
- Subjects
- *
NEURONS , *ANXIETY , *COGNITIVE ability , *NEURAL circuitry , *HIPPOCAMPUS (Brain) - Abstract
Cholinergic neurons in the medial septum (MS) participate in various cognitive and emotional behaviors, including innate anxiety. Chronic pain involves perceptual, cognitive and emotional components. Whether MS cholinergic system modulates pain-induced anxiety and the underlying neural circuits are involved remain unclear. In the present study, we showed that chemogenetic (DREADD) inhibition of MS cholinergic neurons relieved pain-induced anxiety-like behaviors in open field and elevated plus maze tests. Inhibiting the MS–rostral anterior cingulate cortex (rACC), but not the MS–ventral hippocampal CA1 pathway, achieved anxiolysis. These findings indicate the involvement of MS cholinergic system in modulating pain-induced anxiety-like behaviors. [ABSTRACT FROM AUTHOR] more...
- Published
- 2018
- Full Text
- View/download PDF
46. The Frontal Area with Higher Frequency Response Is the Principal Feature of Laser-Evoked Potentials in Rats with Chronic Inflammatory Pain: A Parallel Factor Analysis Study
- Author
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Jing Wang, Juan Wang, You Wan, and Xiaoli Li
- Subjects
chronic inflammatory pain ,event-related potentials ,parallel factor analysis ,wavelet transform ,rat ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Chronic pain is a pathological developing course of pain. In clinic, an objective indicator is needed for diagnosing and better controlling chronic pain. The abnormal neural responses in chronic pain are reflected by multiple event-related potentials (ERPs) in time, frequency, and location domain, respectively. However, multiple changes in ERPs are not applicable in clinic. So, the principal feature covered the most informative changes extracted from these three domains of ERP during the development of chronic pain is needed. In the present study, a parallel factor analysis method was employed to extract time–frequency–channel features of laser-evoked potential (LEP) simultaneously from rats with chronic inflammatory pain. Results showed that the main feature of LEP in channel domain locates in the frontal brain region in rats with chronic inflammatory pain while in the parietal brain region in control rats. In the frequency domain, the main frequency of LEP was significantly higher in chronic inflammatory pain rats than that in control rats. These findings indicate that the frontal region with higher frequency response to nociceptive information is the principal feature in the chronic pain state. Our study provided not only a principal feature of LEP but also a promising strategy for chronic pain, which is potential for clinic application. more...
- Published
- 2017
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47. Pain aversion and anxiety-like behavior occur at different times during the course of chronic inflammatory pain in rats.
- Author
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Yuanyuan Wu, Xinmiao Yao, Yongliang Jiang, Xiaofen He, Xiaomei Shao, Junying Du, Zui Shen, Qiaoying He, and Jianqiao Fang
- Subjects
ANXIETY ,PAIN tolerance ,PAIN management ,CHRONIC pain treatment ,ALLODYNIA - Abstract
Pain is considered a multidimensional conscious experience that includes a sensory component and a negative affective-motivational component. The negative affective-motivational component of pain is different from the sensory component and amplifies the pain experience. Nowadays, a significant number of preclinical research groups have focused their attention on the affective symptoms of pain. In the present study, we investigated the pain aversion and anxiety like behavior of the complete Freund's adjuvant (CFA)-induced chronic pain model. CFA rats experienced spontaneous pain during pain-paired conditioning (pain aversion) and spontaneous pain produces an affective response (anxiety-like behavior). Moreover, pain aversion was gradually attenuated, while the anxiety-like behavior increased in 4 weeks. Therefore, although the negative effect (including pain aversion and anxiety) is always associated with hyperalgesia, the manifestations of negative effect may follow different time courses, which may influence the progress of primary disease. The findings illustrate that targeted therapy should focus on a specific aspect in different stages of pain. Our study emphasizes the necessity of using multiple tests to study pain comorbidities. [ABSTRACT FROM AUTHOR] more...
- Published
- 2017
- Full Text
- View/download PDF
48. Electroacupuncture attenuates chronic inflammatory pain and depression comorbidity by inhibiting hippocampal neuronal apoptosis via the PI3K/Akt signaling pathway.
- Author
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Yang, Pu, Chen, Haiyan, Wang, Tian, Li, Ling, Su, Hong, Li, Jing, He, Yujun, and Su, Shengyong
- Subjects
- *
PI3K/AKT pathway , *CELLULAR signal transduction , *ELECTROACUPUNCTURE , *CHRONIC pain , *NEURONS - Abstract
• Two injections of CFA can induce pain sensitivity and depression-like behavior in adult male SD rats. • CFA leads to pathological morphological changes and increased apoptosis in the hippocampal tissue of rats, as well as inhibition of the PI3K/Akt pathway. • Both electrical acupuncture and duloxetine can activate the PI3K/Akt signaling pathway, reduce hippocampal neuronal apoptosis, and improve pain and depression-like behavior. In chronic inflammatory pain (CIP) and depression, neuroapoptosis has been identified as a contributing factor. Electroacupuncture (EA) shows promise as an alternative therapy for this comorbidity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of EA on hippocampal neuronal apoptosis in rats with CIP and depression. Rats received plantar injections of complete Freund's adjuvant (CFA) on days 0 and 14. They were then divided into groups: sham operation, model, EA, and duloxetine. EA was administered at Hegu (LI4) and Taichong (LR3) from days 15 to 28, while the duloxetine group received duloxetine and distilled water daily (0.1 mg/ml). Pain behavior was assessed using the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests. Depression-like behavior was evaluated through the sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). Hematoxylin and eosin (HE) staining was employed to assess pathological changes in the hippocampus. Nerve cell apoptosis was determined using TUNEL fluorescence staining. Western blot analysis was conducted to measure the protein expression of Bcl-2, Bax, p-PI3K/PI3K, and p-Akt/Akt. EA demonstrated significant pain intensity reduction and alleviation of pain-related depressive symptoms. Our findings from the HE staining confirmed that CIP induced by CFA led to morphological changes in the hippocampus, while EA effectively reversed these pathological alterations. Moreover, EA intervention remarkably reduced neuronal apoptosis and exhibited an upregulation of Bcl-2 protein expression accompanied by a decrease in Bax expression. Additionally, EA activated the PI3K/Akt signaling pathway. Overall, our study suggests that EA holds the potential to improve pain and depressive behaviors in rats with CIP and depression comorbidity, potentially mediated through the activation of the PI3K/Akt pathway, leading to a reduction in hippocampal neuronal apoptosis. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
- Full Text
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49. Dimethylheptyl-THC-11-oic Acid : A Nonpsychoactive Antiinflammatory Agent with a Cannabinoid Template Structure
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Zurier, Robert B., Rossetti, Ronald G., Lane, Joan H., Goldberg, John M., Hunter, Sheila A., Burstein, Sumner H., Nahas, Gabriel G., editor, Sutin, Kenneth M., editor, Harvey, David, editor, Agurell, Stig, editor, Pace, Nicholas, editor, and Cancro, Robert, editor more...
- Published
- 1999
- Full Text
- View/download PDF
50. Gastrodin relieved complete Freund's adjuvant-induced spontaneous pain by inhibiting inflammatory response.
- Author
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Sun, Ting, Wang, Jian, Li, Xiang, Li, Yu-Jiao, Feng, Dan, Shi, Wen-Long, Zhao, Ming-Gao, Wang, Jian-Bo, and Wu, Yu-Mei
- Subjects
- *
GASTRODIA elata , *INFLAMMATION prevention , *PAIN management , *NEUROPLASTICITY , *TUMOR necrosis factors , *THERAPEUTICS - Abstract
The analgesic effects of gastrodin (GAS), an active component derived from the Chinese herb Tian ma ( Gastrodia elata Blume ), on chronic inflammatory pain of mice and the involved molecular mechanisms were investigated. GAS significantly attenuated mice chronic inflammatory pain induced by hindpaw injection of complete Freund's adjuvant (CFA) and the accompanying anxiety-like behaviors. GAS administration reduced CFA-induced up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, GluN2A- and GluN2B-containing N -methyl- d -aspartate (NMDA) receptors, and Ca 2 + /calmodulin-dependent protein kinase II-alpha (CaMKII-α) in the anterior cingulate cortex (ACC). The GluN2A and GluN2B subunits of NMDA receptors, the GluR1 type of AMPA receptor, and CaMKII-α are key molecules responsible for neuroplasticity involved in chronic pain and the accompanying anxiety. Moreover, GAS administration reduced the activation of astrocyte and microglia and the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice. Therefore, GAS administration relieved chronic pain, exerted anxiolytic effects by regulating neuroplasticity molecules, and attenuated the inflammatory response by reducing the induction of TNF-α and IL-6 in the ACC of the CFA-injected mice. [ABSTRACT FROM AUTHOR] more...
- Published
- 2016
- Full Text
- View/download PDF
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