Conclusions
Deletion of TRPC5 receptor signalling is associated with exacerbation of pain-like behaviour in OA which correlates with increased expression of enzymes involved in extracellular remodelling, inflammatory cells in the synovium and increased neuronal activation and injury in DRG. Together, these results identify a modulating role for TRPC5 in OA-induced pain-like behaviours.
Results
TRPC5 KO mice developed a discrete enhanced pain-related phenotype. In the MIA model, the pain-related phenotype correlated with c-Fos expression in the dorsal horn and increased expression of nerve injury markers ATF3, CSF1 and galanin in the ipsilateral DRG. There were negligible differences in the joint pathology between WT and TRPC5 KO mice, however detailed gene expression analysis determined increased expression of the mast cell marker CD117 as well as extracellular matrix remodelling proteinases MMP2, MMP13 and ADAMTS4 in MIA-treated TRPC5 KO mice. TRPC5 expression was defined to sensory subpopulations in DRG. Conclusions: Deletion of TRPC5 receptor signalling is associated with exacerbation of pain-like behaviour in OA which correlates with increased expression of enzymes involved in extracellular remodelling, inflammatory cells in the synovium and increased neuronal activation and injury in DRG. Together, these results identify a modulating role for TRPC5 in OA-induced pain-like behaviours.