Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs
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 disea...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2020.00077/full |
| _version_ | 1818542705740873728 |
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| author | Laura Minnema Laura Minnema Joshua Wheeler Joshua Wheeler Masataka Enomoto Masataka Enomoto Saumitra Pitake Santosh K. Mishra Santosh K. Mishra B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles |
| author_facet | Laura Minnema Laura Minnema Joshua Wheeler Joshua Wheeler Masataka Enomoto Masataka Enomoto Saumitra Pitake Santosh K. Mishra Santosh K. Mishra B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles |
| author_sort | Laura Minnema |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T22:25:38Z |
| format | Article |
| id | doaj.art-0cd621a3788447798af596afa1ac8c2d |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-11T22:25:38Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-0cd621a3788447798af596afa1ac8c2d2022-12-22T00:48:17ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-02-011410.3389/fnins.2020.00077507265Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in DogsLaura Minnema0Laura Minnema1Joshua Wheeler2Joshua Wheeler3Masataka Enomoto4Masataka Enomoto5Saumitra Pitake6Santosh K. Mishra7Santosh K. Mishra8B. Duncan X. Lascelles9B. Duncan X. Lascelles10B. Duncan X. Lascelles11B. Duncan X. Lascelles12Translational Research in Pain Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Pain Research and Education Center, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesTranslational Research in Pain Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Pain Research and Education Center, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Pain Research and Education Center, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesTranslational Research in Pain Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Pain Research and Education Center, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesThurston Arthritis Research Center, UNC School of Medicine, Chapel Hill, NC, United StatesCenter for Translational Pain Research, Department of Anesthesiology, Duke University, Durham, NC, United StatesArthritis, 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.https://www.frontiersin.org/article/10.3389/fnins.2020.00077/fullosteoarthritispainDRGGDNFarteminGFRα3 |
| spellingShingle | Laura Minnema Laura Minnema Joshua Wheeler Joshua Wheeler Masataka Enomoto Masataka Enomoto Saumitra Pitake Santosh K. Mishra Santosh K. Mishra B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs Frontiers in Neuroscience osteoarthritis pain DRG GDNF artemin GFRα3 |
| title | Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs |
| title_full | Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs |
| title_fullStr | Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs |
| title_full_unstemmed | Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs |
| title_short | Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs |
| title_sort | correlation of artemin and gfrα3 with osteoarthritis pain early evidence from naturally occurring osteoarthritis associated chronic pain in dogs |
| topic | osteoarthritis pain DRG GDNF artemin GFRα3 |
| url | https://www.frontiersin.org/article/10.3389/fnins.2020.00077/full |
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