Arthritis is a debilitating condition characterised by chronic pain in and around the joint. Sensory nerves that contain and release neuropeptides innervate the joint and play a major role in mediating pain. We are interested in the role of the transient receptor potential (TRP) channels, that are calcium-permeable cation channels in mediating the pain and inflammation that occur in the joint during arthritis. We have used TNF and CFA murine models of joint inflammation to elucidate mechanisms. Our early work investigated the role of TRPV1, a channel that is localised to sensory nerves and best known for its activation by the chilli pepper extract capsaicin, noxious heat as well as certain lipids. Studies in TRPV1 knockout mice revealed that CFA thermal pain was alleviated, but TNF levels remained high. TRPA1 is a second TRP channel localised to TPRV1-containing sensory nerves. TRPA1 is activated, amongst other things, by noxious cold and reactive oxygen species. TRPA1 mediates pain in arthritis, as demonstrated by studies including from our laboratory, in a number of species. We have shown that TRPA1 is a vascular cold sensor, also that mice demonstrate exacerbated CFA-induced joint pain after environmental cold exposure. Finally we have now discovered evidence of a regulatory role for the TRPC5 receptor, in that TRPC5KO mice exhibit an enhanced inflammation that is mirrored in WT mice treated with a TRPC5 antagonist.
Thus there is compelling evidence that TRP receptors have potential roles in mediating pain, and in some cases the inflammation, in arthritis. They can act via pro-inflammatory and anti-inflammatory mechanisms, depending on subtype. These effects appear to depend on the TRP channels, with some evidence that the neuropeptides are also involved in pain processing.
Disclosure of Interest None declared
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