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Minnema L, Wheeler J, Enomoto M, et al. Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs. Front Neurosci. 2020;14:77doi: 10.3389/fnins.2020.00077.
Minnema, L., Wheeler, J., Enomoto, M., Pitake, S., Mishra, S. K., & Lascelles, B. D. X. (2020). Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs. Frontiers in neuroscience, 1477. https://doi.org/10.3389/fnins.2020.00077
Minnema, Laura, et al. "Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs." Frontiers in neuroscience vol. 14 (2020): 77. doi: https://doi.org/10.3389/fnins.2020.00077
Minnema L, Wheeler J, Enomoto M, Pitake S, Mishra SK, Lascelles BDX. Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs. Front Neurosci. 2020 Feb 13;14:77. doi: 10.3389/fnins.2020.00077. eCollection 2020. PMID: 32116521; PMCID: PMC7031206.
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Front Neurosci. 2020 Feb 13;14:77. doi: 10.3389/fnins.2020.00077. eCollection 2020.

Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs.

Frontiers in neuroscience

Laura Minnema, Joshua Wheeler, Masataka Enomoto, Saumitra Pitake, Santosh K Mishra, B Duncan X Lascelles

Affiliations

  1. Translational Research in Pain Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  2. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  3. Comparative Pain Research and Education Center, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  4. Thurston Arthritis Research Center, UNC School of Medicine, Chapel Hill, NC, United States.
  5. Center for Translational Pain Research, Department of Anesthesiology, Duke University, Durham, NC, United States.

PMID: 32116521 PMCID: PMC7031206 DOI: 10.3389/fnins.2020.00077

Abstract

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 (GFRα3), 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 GFRα3 might be associated with OA pain. Our results using banked tissue from well-phenotyped dogs indicates that artemin/GFRα3 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/GFRα3 signaling pathway may be important in OA pain in both non-humans and humans and may ultimately lead to novel therapeutics.

Copyright © 2020 Minnema, Wheeler, Enomoto, Pitake, Mishra and Lascelles.

Keywords: DRG; GDNF; GFRα3; artemin; dogs; human; osteoarthritis; pain

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