Osteoarthritic tissues modulate functional properties of sensory neurons associated with symptomatic OA pain |
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| Authors: | Xin Li Jae-Sung Kim Andre J van Wijnen Hee-Jeong Im |
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| Institution: | (1) Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA;(2) Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA;(3) Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA;(4) Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA; |
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| Abstract: | Osteoarthritis (OA) is an age-related degenerative disease of cartilaginous tissues that is accompanied by hyperalgesia. Molecular
cause and effect relationships between OA and pain remain to be elucidated. In this study, we have developed an experimental
ex vivo organ co-culture system with dorsal root ganglia (DRGs) and knee synovial tissues from OA patients or unaffected human
subjects. Our results suggest that tissues may generate symptomatic pain by altering the functional properties of sensory
neurons. Specifically, we find that the expression levels of genes associated with neuronal pathways (e.g., SP, NK1, NK2,
NPYR1, NPYR2, α2δ1) or inflammation (COX2/PTGS2 and IL6/interferon β2) are clearly elevated in DRG explants cultured in the
presence of OA derived synovial tissues. These findings are consistent with a model in which cytokines and pain molecules
produced by knee synovium sensitize nociceptive neurons in tissues peripheral to joint cartilage. |
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