Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain
Osteoarthritis (OA) associated pain (OA-pain) is a significant global problem. OA-pain limits limb use and mobility and is associated with widespread sensitivity. Therapeutic options are limited, and the available options are often associated with adverse effects. The lack of therapeutic options is...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.738976/full |
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| author | Laura Minnema Ankita Gupta Ankita Gupta Santosh K. Mishra Santosh K. Mishra B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles |
| author_facet | Laura Minnema Ankita Gupta Ankita Gupta Santosh K. Mishra Santosh K. Mishra B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles |
| author_sort | Laura Minnema |
| collection | DOAJ |
| description | Osteoarthritis (OA) associated pain (OA-pain) is a significant global problem. OA-pain limits limb use and mobility and is associated with widespread sensitivity. Therapeutic options are limited, and the available options are often associated with adverse effects. The lack of therapeutic options is partly due to a lack of understanding of clinically relevant underlying neural mechanisms of OA-pain. In previous work in naturally occurring OA-pain in dogs, we identified potential signaling molecules (artemin/GFRα3) that were upregulated. Here, we use multiple approaches, including cellular, mouse genetic, immunological suppression in a mouse model of OA, and clinically relevant measures of sensitivity and limb use to explore the functional role of artemin/GFRα3 signaling in OA-pain. We found the monoiodoacetate (MIA)-induced OA-pain in mice is associated with decreased limb use and hypersensitivity. Exogenous artemin induces mechanical, heat, and cold hypersensitivity, and systemic intraperitoneal anti-artemin monoclonal antibody administration reverses this hypersensitivity and restores limb use in mice with MIA-induced OA-pain. An artemin receptor GFRα3 expression is increased in sensory neurons in the MIA model. Our results provide a molecular basis of arthritis pain linked with artemin/GFRα3 signaling and indicate that further work is warranted to investigate the neuronal plasticity and the pathways that drive pain in OA. |
| first_indexed | 2024-12-20T11:11:58Z |
| format | Article |
| id | doaj.art-3ba76ba42a0b45369aa9586c11660597 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-20T11:11:58Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-3ba76ba42a0b45369aa9586c116605972022-12-21T19:42:43ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-01-011610.3389/fnins.2022.738976738976Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis PainLaura Minnema0Ankita Gupta1Ankita Gupta2Santosh K. Mishra3Santosh K. Mishra4B. Duncan X. Lascelles5B. Duncan X. Lascelles6B. Duncan X. Lascelles7B. Duncan X. Lascelles8B. Duncan X. Lascelles9Translational Research in Pain Program, Department of Clinical Sciences, 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 StatesDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesDepartment of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Pain Research and Education Center, 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 StatesDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United StatesComparative Pain Research and Education Center, North Carolina State University, Raleigh, NC, United StatesThurston Arthritis Center, UNC School of Medicine, Chapel Hill, NC, United StatesThurston Arthritis Center, UNC School of Medicine, Chapel Hill, NC, United StatesOsteoarthritis (OA) associated pain (OA-pain) is a significant global problem. OA-pain limits limb use and mobility and is associated with widespread sensitivity. Therapeutic options are limited, and the available options are often associated with adverse effects. The lack of therapeutic options is partly due to a lack of understanding of clinically relevant underlying neural mechanisms of OA-pain. In previous work in naturally occurring OA-pain in dogs, we identified potential signaling molecules (artemin/GFRα3) that were upregulated. Here, we use multiple approaches, including cellular, mouse genetic, immunological suppression in a mouse model of OA, and clinically relevant measures of sensitivity and limb use to explore the functional role of artemin/GFRα3 signaling in OA-pain. We found the monoiodoacetate (MIA)-induced OA-pain in mice is associated with decreased limb use and hypersensitivity. Exogenous artemin induces mechanical, heat, and cold hypersensitivity, and systemic intraperitoneal anti-artemin monoclonal antibody administration reverses this hypersensitivity and restores limb use in mice with MIA-induced OA-pain. An artemin receptor GFRα3 expression is increased in sensory neurons in the MIA model. Our results provide a molecular basis of arthritis pain linked with artemin/GFRα3 signaling and indicate that further work is warranted to investigate the neuronal plasticity and the pathways that drive pain in OA.https://www.frontiersin.org/articles/10.3389/fnins.2022.738976/fullpainosteoarthritis (OA)arteminGFRα3TRPV1monoiodoacetate (MIA) |
| spellingShingle | Laura Minnema Ankita Gupta Ankita Gupta Santosh K. Mishra Santosh K. Mishra B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles B. Duncan X. Lascelles Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain Frontiers in Neuroscience pain osteoarthritis (OA) artemin GFRα3 TRPV1 monoiodoacetate (MIA) |
| title | Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain |
| title_full | Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain |
| title_fullStr | Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain |
| title_full_unstemmed | Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain |
| title_short | Investigating the Role of Artemin and Its Cognate Receptor, GFRα3, in Osteoarthritis Pain |
| title_sort | investigating the role of artemin and its cognate receptor gfrα3 in osteoarthritis pain |
| topic | pain osteoarthritis (OA) artemin GFRα3 TRPV1 monoiodoacetate (MIA) |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.738976/full |
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