Osteoarthritic symptom is the key reason to seek medical assistance, yet there is no effective way to relieve osteoarthritis (OA)-induced pain. Our long term goal is to understand the discrepancy between the degree of cartilage degeneration and the actual experience of joint pain by investigating the neuroanatomical approaches in an experimental OA model followed by validation in human joint tissues. We propose that OA pain sensation can develop independently of progressive cartilage degeneration, and that severity of joint pain is due to cellular and molecular plasticity in the sensory neurons of the innervating dorsal root ganglion and pathological changes in synovium (e.g., synovitis, angiogenesis). We will identify the fundamental factors that facilitate pro- nociception in OA independently of the degree of cartilage degeneration. Our studies will also provide important empirical support for the development of clinical strategies to treat OA symptoms. Our results will provide a novel view of major disease-modified chronic pain mechanisms that accompany degeneration of knee joints in OA. At a broader level, results from this proposal will impact our conceptual perspectives and future research translation by clarifying relationships between musculoskeletal tissue degeneration and debilitating OA symptoms.

Public Health Relevance

(Relevance). This application provides a unique opportunity to study nociceptive pathway initiated by osteoarthritis by combining genetically modified mice and an established translational animal model that are amenable to behavioral pain tests that have set the stage for rapid advances in this highly under-studied area. We address a fundamental question: 'Why is there no close correlation between the degree of cartilage degeneration and the degree of pain sensation? 'Our results will discover a novel neuroanatomical mechanism-based nociceptive pathway and molecular mechanisms that cannot be addressed by clinical protocols in humans, and will establish new experimental avenues and novel research directions for osteoarthritis -caused knee joint pain. PHS 398 (Rev. 11/07) Page 1

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01BX002647-04
Application #
9505844
Study Section
Endocrinology B (ENDB)
Project Start
2014-10-01
Project End
2018-09-30
Budget Start
2017-10-01
Budget End
2018-09-30
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Jesse Brown VA Medical Center
Department
Type
DUNS #
010299204
City
Chicago
State
IL
Country
United States
Zip Code
60612
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Im, Hee-Jin; Baek, Shin-Hye; Chu, Min Kyung et al. (2017) Association Between Weekend Catch-up Sleep and Lower Body Mass: Population-Based Study. Sleep 40:
Kroin, Jeffrey S; Kc, Ranjan; Li, Xin et al. (2016) Intraarticular slow-release triamcinolone acetate reduces allodynia in an experimental mouse knee osteoarthritis model. Gene 591:1-5
Im, Hyung-Jun; Hahm, Jarang; Kang, Hyejin et al. (2016) Disrupted brain metabolic connectivity in a 6-OHDA-induced mouse model of Parkinson's disease examined using persistent homology-based analysis. Sci Rep 6:33875
Lewallen, Eric A; Bonin, Carolina A; Li, Xin et al. (2016) The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes. Gene 591:456-64
Kc, Ranjan; Li, Xin; Kroin, Jeffrey S et al. (2016) PKC? null mutations in a mouse model of osteoarthritis alter osteoarthritic pain independently of joint pathology by augmenting NGF/TrkA-induced axonal outgrowth. Ann Rheum Dis 75:2133-2141
Dudek, Michal; Gossan, Nicole; Yang, Nan et al. (2016) The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity. J Clin Invest 126:365-76
Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok et al. (2016) A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver. Cancer Res 76:1698-704
Hamilton, John L; Nagao, Masashi; Levine, Brett R et al. (2016) Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain. J Bone Miner Res 31:911-24

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