8 results on '"Chronic neuropathic pain"'
Search Results
2. Divanillyl sulfone suppresses NLRP3 inflammasome activation via inducing mitophagy to ameliorate chronic neuropathic pain in mice.
- Author
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Shao, Shuai, Xu, Cheng-Bo, Chen, Cheng-Juan, Shi, Gao-Na, Guo, Qing-Lan, Zhou, Yu, Wei, Ya-Zi, Wu, Lei, Shi, Jian-Gong, and Zhang, Tian-Tai
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NEURALGIA , *NLRP3 protein , *INFLAMMASOMES , *CHRONIC pain , *SCIATIC nerve injuries , *INTRATHECAL injections , *LABORATORY mice - Abstract
Background: Chronic neuropathic pain is a frequent sequel to peripheral nerve injury and maladaptive nervous system function. Divanillyl sulfone (DS), a novel structural derivative of 4,4'-dihydroxydibenzyl sulfoxide from a traditional Chinese medicine Gastrodia elata with anti-nociceptive effects, significantly alleviated neuropathic pain following intrathecal injection. Here, we aimed to investigate the underlying mechanisms of DS against neuropathic pain.Methods: A chronic constrictive injury (CCI) mouse model of neuropathic pain induced by sciatic nerve ligation was performed to evaluate the effect of DS by measuring the limb withdrawal using Von Frey filament test. Immunofluorescence staining was used to assess the cell localizations and expressions of Iba-1, ASC, NLRP3, and ROS, the formation of autolysosome. The levels of NLRP3-related proteins (caspase-1, NLRP3, and IL-1β), mitophagy-related proteins (LC3, Beclin-1, and p62), and apoptosis-related proteins (Bcl-XL and Bax) were detected by Western blotting. The apoptosis of BV-2 cell and caspase activity were evaluated by flow cytometry.Results: DS significantly alleviated the neuropathic pain by increasing the mechanical withdrawal threshold and inhibiting the activation of NLRP3 in CCI-induced model mice. Our findings indicated that DS promoted the mitophagy by increasing the LC3II and Beclin 1 and decreasing the levels of p62 protein in BV-2 cell. This is accompanied by the inhibition of NLRP3 activation, which was shown as inhibited the expression of NLRP3 in lysates as well as the secretion of mature caspase-1 p10 and IL-1β p17 in supernatants in cultured BV-2 microglia. In addition, DS could promote mitophagy-induced improvement of dysfunctional mitochondria by clearing intracellular ROS and restoring mitochondrial membrane potential.Conclusion: Together, our findings demonstrated that DS ameliorate chronic neuropathic pain in mice by suppressing NLRP3 inflammasome activation induced by mitophagy in microglia. DS may be a promising therapeutic agent for chronic neuropathic pain. [ABSTRACT FROM AUTHOR] more...- Published
- 2021
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3. Sexual dimorphism in cognitive disorders in a murine model of neuropathic pain.
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Won, Soonmi, Park, Keebum, Lim, Hyoungsub, and Lee, Sung Joong
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SEXUAL dimorphism , *COGNITION disorders , *INTELLIGENCE tests , *CHRONIC pain , *SPINAL nerves , *PAIN - Abstract
Background: A sex-difference in susceptibility to chronic pain is well-known. Although recent studies have begun to reveal the sex-dependent mechanisms of nerve injury-induced pain sensitization, sex differences in the affective and cognitive brain dysfunctions associated with chronic pain have not been investigated. Therefore, we tested whether chronic pain leads to affective and cognitive disorders in a mouse neuropathic pain model and whether those disorders are sexually dimorphic. Methods: Chronic neuropathic pain was induced in male and female mice by L5 spinal nerve transection (SNT) injury. Pain sensitivity was measured with the von Frey test. Affective behaviors such as depression and anxiety were assessed by the forced swim, tail suspension, and open field tests. Cognitive brain function was assessed with the Morris water maze and the novel object location and novel object recognition tests. Results: Mechanical allodynia was induced and maintained for up to 8 weeks after SNT in both male and female mice. Depressive- and anxiety-like behaviors were observed 8 weeks post-SNT injury regardless of sex. Chronic pain-induced cognitive deficits measured with the Morris water maze and novel object location test were seen only in male mice, not in female mice. Conclusions: Chronic neuropathic pain is accompanied by anxiety- and depressive-like behaviors in a mouse model regardless of sex, and male mice are more vulnerable than female mice to chronic pain-associated cognitive deficits. [ABSTRACT FROM AUTHOR] more...
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- 2020
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4. Repeated electroacupuncture treatment attenuated hyperalgesia through suppression of spinal glial activation in chronic neuropathic pain rats.
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Jun-ying Wang, Yong-hui Gao, Li-na Qiao, Jian-liang Zhang, Cheng-Lin Duan-mu, Ya-xia Yan, Shu-ping Chen, and Jun-ling Liu
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CHRONIC pain treatment ,SCIATIC nerve injuries ,HYPERALGESIA treatment ,ANIMAL experimentation ,ELECTROACUPUNCTURE ,FLUORESCENT antibody technique ,GENE expression ,NEURALGIA ,NEUROGLIA ,RATS ,STATISTICAL sampling ,STAINS & staining (Microscopy) ,PAIN threshold ,THERAPEUTICS - Abstract
Background: Cumulated evidence reveals that glial cells in the spinal cord play an important role in the development of chronic neuropathic pain and are also complicated in the analgesic effect of EA intervention. But the roles of microgliacytes and astrocytes of spinal cord in the process of EA analgesia remain unknown. Methods: A total of 120 male Wistar rats were used in the present study. The neuropathic pain model was established by chronic constrictive injury (CCI) of the sciatic nerve. The rats were randomly divided into sham group, CCI group, and sham CCI + EA group, and CCI + EA group. EA was applied to bilateral Zusanli (ST36)-Yanlingquan (GB34). The mechanical (both time and force responses) and thermal pain thresholds (PTs) of the bilateral hind-paws were measured. The number of microgliacytes and activity of astrocytes in the dorsal horns (DHs) of lumbar spinal cord (L4-5) were examined by immunofluorescence staining, and the expression of glial fibrillary acidic protein (GFAP) protein was detected by western blot. Results: Following CCI, both mechanical and thermal PTs of the ipsilateral hind-paw were significantly decreased beginning from the 3rd day after surgery (P < 0.05), and the mechanical PT of the contralateral hind-paw was considerably decreased from the 6th day on after surgery (P < 0.05). CCI also significantly upregulated the number of Iba-1 labeled microgliacytes and the fluorescence intensity of glial fibrillary acidic protein (GFAP) -labeled astrocyte in the superficial laminae of DHs on bilateral sides (P < 0.05). After repeated EA, the mechanical and thermal PTs at bilateral hind-paws were significantly relieved (P < 0.05). The increased of number of microgliacytes was markedly suppressed by 2 days' EA intervention, and the average fluorescence intensity was suppressed by 2 weeks' EA. The expression of GFAP protein were down-regulated by 1 and 2 weeks' EA treatment, respectively (P < 0.05). Conclusions: Repeated EA can relieve neuropathic pain and mirror-image pain in chronic neuropathic pain rats, which is probably associated with its effect in downregulating glial cell activation of the lumbar spinal cord, the microgliacyte first and astrocyte later. [ABSTRACT FROM AUTHOR] more...
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- 2018
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5. Alleviation of chronic neuropathic pain by environmental enrichment in mice well after the establishment of chronic pain.
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Vachon, Pascal, Millecamps, Magali, Low, Lucie, Thompsosn, Scott J., Pailleux, Floriane, Beaudry, Francis, Bushnell, Catherine M., and Stone, Laura S.
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CHRONIC pain , *LABORATORY mice , *NEUROPEPTIDES , *MASS spectrometry , *PHENOTYPES - Abstract
Background: In animal models, the impact of social and environmental manipulations on chronic pain have been investigated in short term studies where enrichment was implemented prior to or concurrently with the injury. The focus of this study was to evaluate the impact of environmental enrichment or impoverishment in mice three months after induction of chronic neuropathic pain. Methods: Thirty-four CD-1 seven to eight week-old male mice were used. Mice underwent surgery on the left leg under isoflurane anesthesia to induce the spared nerve injury model of neuropathic pain or sham condition. Mice were then randomly assigned to one of four groups: nerve injury with enriched environment (n = 9), nerve injury with impoverished environment (n = 8), sham surgery with enriched environment (n = 9), or sham surgery with impoverished environment (n = 8). The effects of environmental manipulations on mechanical (von Frey filaments) heat (hot plate) and cold (acetone test) cutaneous hypersensitivities, motor impairment (Rotarod), spontaneous exploratory behavior (open field test), anxiety-like behavior (elevated plus maze) and depression-like phenotype (tail suspension test) were assessed in neuropathic and control mice 1 and 2 months post-environmental change. Finally, the effect of the environment on spinal expression of the pro-nociceptive neuropeptides substance P and CGRP form the lumbar spinal cord collected at the end of the study was evaluated by tandem liquid chromatography mass spectrometry. Results: Environmental enrichment attenuated nerve injury-induced hypersensitivity to mechanical and cold stimuli. In contrast, an impoverished environment exacerbated mechanical hypersensitivity. No antidepressant effects of enrichment were observed in animals with chronic neuropathic pain. Finally, environmental enrichment resulted lower SP and CGRP concentrations in neuropathic animals compared to impoverishment. These effects were all observed in animals that had been neuropathic for several months prior to intervention. Conclusions: These results suggest that environmental factors could play an important role in the rehabilitation of chronic pain patients well after the establishment of chronic pain. Enrichment is a potentially inexpensive, safe and easily implemented non-pharmacological intervention for the treatment of chronic pain. [ABSTRACT FROM AUTHOR] more...
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- 2013
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6. Unilateral L4-dorsal root ganglion stimulation evokes pain relief in chronic neuropathic postsurgical knee pain and changes of inflammatory markers: part II whole transcriptome profiling
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Kinfe, Thomas M., Asif, Maria, Chakravarthy, Krishnan V., Deer, Timothy R., Kramer, Jeffery M., Yearwood, Thomas L., Hurlemann, Rene, Hussain, Muhammad Sajid, Motameny, Susanne, Wagle, Prerana, Nürnberg, Peter, Gravius, Sascha, Randau, Thomas, Gravius, Nadine, Chaudhry, Shafqat R., and Muhammad, Sajjad more...
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- 2019
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7. Unilateral L4-dorsal root ganglion stimulation evokes pain relief in chronic neuropathic postsurgical knee pain and changes of inflammatory markers: part II whole transcriptome profiling
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Sajjad Muhammad, Krishnan Chakravarthy, M. Asif, Susanne Motameny, Jeffery M. Kramer, Thomas L. Yearwood, Thomas M. Kinfe, Thomas M. Randau, Nadine Gravius, Timothy R. Deer, Sascha Gravius, Prerana Wagle, Peter Nürnberg, René Hurlemann, Shafqat Rasul Chaudhry, Muhammad Sajid Hussain, HUS Neurocenter, Clinicum, Neurokirurgian yksikkö, and University of Helsinki more...
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0301 basic medicine ,Male ,Chemokine ,SPINAL-CORD STIMULATION ,lcsh:Medicine ,3124 Neurology and psychiatry ,Transcriptome ,0302 clinical medicine ,Dorsal root ganglion ,ANIMAL-MODEL ,Ganglia, Spinal ,GENE-EXPRESSION ,Pain, Postoperative ,biology ,General Medicine ,Middle Aged ,Pathophysiology ,Complex regional pain syndrome ,medicine.anatomical_structure ,Transcutaneous Electric Nerve Stimulation ,Cytokines ,Interleukin 18 ,Female ,medicine.symptom ,Chronic Pain ,Inflammation Mediators ,Gonadotropin-releasing hormone receptor ,Metabolic Networks and Pathways ,Inflammation ,Chronic neuropathic pain ,Dorsal root ganglion stimulation ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,medicine ,Humans ,Pain Management ,Knee ,Saliva ,Aged ,business.industry ,Research ,Gene Expression Profiling ,lcsh:R ,3112 Neurosciences ,medicine.disease ,030104 developmental biology ,Immunology ,biology.protein ,Neuralgia ,3111 Biomedicine ,Gene expression ,business ,030217 neurology & neurosurgery ,Biomarkers ,Complex Regional Pain Syndromes - Abstract
Background In our recent clinical trial, increased peripheral concentrations of pro-inflammatory molecular mediators were determined in complex regional pain syndrome (CRPS) patients. After 3 months adjunctive unilateral, selective L4 dorsal root ganglion stimulation (L4-DRGSTIM), significantly decreased serum IL-10 and increased saliva oxytocin levels were assessed along with an improved pain and functional state. The current study extended molecular profiling towards gene expression analysis of genes known to be involved in the gonadotropin releasing hormone receptor and neuroinflammatory (cytokines/chemokines) signaling pathways. Methods Blood samples were collected from 12 CRPS patients for whole-transcriptome profiling in order to assay 18,845 inflammation-associated genes from frozen blood at baseline and after 3 months L4-DRGSTIM using PANTHER™ pathway enrichment analysis tool. Results Pathway enrichment analyses tools (GOrilla™ and PANTHER™) showed predominant involvement of inflammation mediated by chemokines/cytokines and gonadotropin releasing hormone receptor pathways. Further, screening of differentially regulated genes showed changes in innate immune response related genes. Transcriptomic analysis showed that 21 genes (predominantly immunoinflammatory) were significantly changed after L4-DRGSTIM. Seven genes including TLR1, FFAR2, IL1RAP, ILRN, C5, PKB and IL18 were down regulated and fourteen genes including CXCL2, CCL11, IL36G, CRP, SCGB1A1, IL-17F, TNFRSF4, PLA2G2A, CREB3L3, ADAMTS12, IL1F10, NOX1, CHIA and BDKRB1 were upregulated. Conclusions In our sub-group analysis of L4-DRGSTIM treated CRPS patients, we found either upregulated or downregulated genes involved in immunoinflammatory circuits relevant for the pathophysiology of CRPS indicating a possible relation. However, large biobank-based approaches are recommended to establish genetic phenotyping as a quantitative outcome measure in CRPS patients. Trial registration The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267 more...
- Published
- 2019
8. Repeated electroacupuncture treatment attenuated hyperalgesia through suppression of spinal glial activation in chronic neuropathic pain rats
- Author
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Wang, Jun-ying, Gao, Yong-hui, Qiao, Li-na, Zhang, Jian-liang, Duan-mu, Cheng-Lin, Yan, Ya-xia, Chen, Shu-ping, and Liu, Jun-ling
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- 2018
- Full Text
- View/download PDF
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