دورية أكاديمية
Studying human nociceptors: from fundamentals to clinic
| العنوان: | Studying human nociceptors: from fundamentals to clinic |
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| المؤلفون: | Middleton, Steven J, Barry, Allison M, Comini, Maddalena, Li, Yan, Ray, Pradipta R, Shiers, Stephanie, Themistocleous, Andreas C, Uhelski, Megan L, Yang, Xun, Dougherty, Patrick M, Price, Theodore J, Bennett, David L |
| المساهمون: | National Institutes of Health, Eugene McDermott Professorship, NIH, Thompson Family Foundation Initiative, H.E.B. Professorship, Wellcome clinical scientist, Wellcome Pain Consortium, European Commission Horizon 2020, International Diabetic Neuropathy Consortium, Novo Nordisk Foundation, Academy of Medical Sciences Starter, Diabetes UK, Medical Research Council, Wellcome, GTC MSDTC Scholarship |
| المصدر: | Brain ; volume 144, issue 5, page 1312-1335 ; ISSN 0006-8950 1460-2156 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2021 |
| الوصف: | Chronic pain affects one in five of the general population and is the third most important cause of disability-adjusted life-years globally. Unfortunately, treatment remains inadequate due to poor efficacy and tolerability. There has been a failure in translating promising preclinical drug targets into clinic use. This reflects challenges across the whole drug development pathway, from preclinical models to trial design. Nociceptors remain an attractive therapeutic target: their sensitization makes an important contribution to many chronic pain states, they are located outside the blood–brain barrier, and they are relatively specific. The past decade has seen significant advances in the techniques available to study human nociceptors, including: the use of corneal confocal microscopy and biopsy samples to observe nociceptor morphology, the culture of human nociceptors (either from surgical or post-mortem tissue or using human induced pluripotent stem cell derived nociceptors), the application of high throughput technologies such as transcriptomics, the in vitro and in vivo electrophysiological characterization through microneurography, and the correlation with pain percepts provided by quantitative sensory testing. Genome editing in human induced pluripotent stem cell-derived nociceptors enables the interrogation of the causal role of genes in the regulation of nociceptor function. Both human and rodent nociceptors are more heterogeneous at a molecular level than previously appreciated, and while we find that there are broad similarities between human and rodent nociceptors there are also important differences involving ion channel function, expression, and cellular excitability. These technological advances have emphasized the maladaptive plastic changes occurring in human nociceptors following injury that contribute to chronic pain. Studying human nociceptors has revealed new therapeutic targets for the suppression of chronic pain and enhanced repair. Cellular models of human nociceptors have enabled ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/brain/awab048 |
| DOI: | 10.1093/brain/awab048/38654049/awab048.pdf |
| الإتاحة: | https://doi.org/10.1093/brain/awab048Test http://academic.oup.com/brain/article-pdf/144/5/1312/38813696/awab048.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.1D60BA1E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/brain/awab048 |
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