Osteoarthritic tissues modulate functional properties of sensory neurons associated with symptomatic OA pain
Department of Cell Biology
Medical Subject Headings
Animals; Coculture Techniques; Ganglia, Spinal; Gene Expression Regulation; Humans; Osteoarthritis; Pain; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells; Synovial Membrane
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, alpha2delta1) or inflammation (COX2/PTGS2 and IL6/interferon beta2) 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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Citation: Mol Biol Rep. 2011 Nov;38(8):5335-9. Epub 2011 Feb 16. Link to article on publisher's site