期刊
FRONTIERS IN NEUROSCIENCE
卷 14, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2020.00077
关键词
osteoarthritis; pain; DRG; GDNF; artemin; GFR alpha 3; dogs; human
资金
- Morris Animal Foundation [D19CA-035]
- College of Veterinary Medicine, North Carolina State University
Arthritis, including osteoarthritis (OA) and other musculoskeletal-associated pain, is a worldwide problem, however, effective drug options are limited. Several receptors, neurotransmitters, and endogenous mediators have been identified in rodent models, but the relevance of these molecules in disease-associated pain is not always clear. Artemin, a neurotrophic factor, and its receptor, glial-derived neurotrophic factor (GDNF) family receptor alpha-3 (GFR alpha 3), have been identified as involved in pain in rodents. Their role in OA-associated pain is unknown. To explore a possible association, we analyzed tissue from naturally occurring OA in dogs to characterize the correlation with chronic pain. We used behavioral assessment, objective measures of limb use, and molecular tools to identify whether artemin and GFR alpha 3 might be associated with OA pain. Our results using banked tissue from well-phenotyped dogs indicates that artemin/GFR alpha 3 may play an important, and hitherto unrecognized, role in chronic OA-associated pain. Elevated serum levels of artemin from osteoarthritic humans compared to healthy individuals suggest translational relevance. Our data provide compelling evidence that the artemin/GFR alpha 3 signaling pathway may be important in OA pain in both non-humans and humans and may ultimately lead to novel therapeutics.
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