自引率: 10.6%
被引量: 37753
通过率: 暂无数据
审稿周期: 5.25
版面费用: 暂无数据
国人发稿量: 13
投稿须知/期刊简介:
This journal is the official publication of the International Association for the Study of Pain and it publishes original research on the nature, mechanisms and treatment of pain. The journal provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.
期刊描述简介:
This journal is the official publication of the International Association for the Study of Pain and it publishes original research on the nature, mechanisms and treatment of pain. The journal provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.
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CARTp/GPR160 mediates behavioral hypersensitivities in mice through NOD2.
Neuropathic pain is a debilitating chronic condition that remains difficult to treat. More efficacious and safer therapeutics are needed. A potential target for therapeutic intervention recently identified by our group is the G-protein coupled receptor 160 (GPR160) and the cocaine- and amphetamine-regulated transcript peptide (CARTp) as a ligand for GPR160. Intrathecal administration of CARTp in rodents causes GPR160-dependent behavioral hypersensitivities. However, the molecular and biochemical mechanisms underpinning GPR160/CARTp-induced behavioral hypersensitivities in the spinal cord remain poorly understood. Therefore, we performed an unbiased RNA transcriptomics screen of dorsal horn spinal cord (DH-SC) tissues harvested at the time of peak CARTp-induced hypersensitivities and identified nucleotide-binding oligomerization domain-containing protein 2 ( Nod2 ) as a gene that is significantly upregulated. Nucleotide-binding oligomerization domain-containing protein 2 is a cytosolic pattern-recognition receptor involved in activating the immune system in response to bacterial pathogens. While NOD2 is well studied under pathogenic conditions, the role of NOD2-mediated responses in nonpathogenic settings is still not well characterized. Genetic and pharmacological approaches reveal that CARTp-induced behavioral hypersensitivities are driven by NOD2, with co-immunoprecipitation studies indicating an interaction between GPR160 and NOD2. Cocaine- and amphetamine-regulated transcript peptide-induced behavioral hypersensitivities are independent of receptor-interacting protein kinase 2 (RIPK2), a common adaptor protein to NOD2. Immunofluorescence studies found NOD2 co-expressed with endothelial cells rather than glial cells, implicating potential roles for CARTp/NOD2 signaling in these cells. While these findings are based only on studies with male mice, our results identify a novel pathway by which CARTp causes behavioral hypersensitivities in the DH-SC through NOD2 and highlights the importance of NOD2-mediated responses in nonpathogenic settings.
被引量：- 发表：1970
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The conotoxin Contulakin-G reverses hypersensitivity observed in rodent models of cancer-induced bone pain without inducing tolerance or motor disturbance.
被引量：- 发表：1970
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Pain mechanistic networks: the development using supervised multivariate data analysis and implications for chronic pain.
被引量：- 发表：1970
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The association between bullying victimization and back pain in young people: a systematic literature review and meta-analysis.
被引量：- 发表：1970
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Development and internal validation of a clinical risk tool to predict chronic postsurgical pain in adults: a prospective multicentre cohort study.
被引量：- 发表：1970
