Background and Purpose: ROS and their downstream molecules such as oxidized phospholipids (OxPL) and 4‐hydroxynonenal activate TRPA1 and TRPV1 (vanilloid 1) cation channels in vivo and in vitro shaping thermal and mechanical hypersensitivity in inflammatory pain. E06/T15 is a monoclonal autoantibody against oxidized phosphatidylcholine (OxPC) used in diagnostics in arteriosclerosis. Recently, we provided evidence that E06 also ameliorates inflammatory pain. Here, we studied E06 for local treatment against hypersensitivity evoked by endogenous and exogenous agonists of TRPA1 or TRPV1 channels.
Experimental Approach: We utilized a combination of reflexive and complex behavioural pain measurements, live‐cell calcium imaging and OxPC‐binding assays. The lipid peroxidation metabolite 4‐hydroxynonenal, hydrogen peroxide as a source of ROS, allyl isothiocyanate and capsaicin were used to activate their respective receptors.
Key Results: All irritants induced thermal and mechanical hypersensitivity, spontaneous nocifensive and affective‐motivational behaviour, as well as calcium influx in HEKTRPA1‐ or HEKTRPV1‐cells and dorsal root ganglion neurons. E06 prevented prolonged mechanical hypersensitivity induced by all irritants except for H2O2. E06 did not alter immediate irritant‐induced nocifensive or affective motivational behaviour. In vitro, E06 blocked only 4‐hydroxynonenal‐induced calcium influx although this compound did not bind to E06. After 1–3 h, all tested irritants elicited formation of OxPC in paw tissue.
Conclusions and Implications: E06 ameliorates not only inflammatory pain but also prolonged hypersensitivity due to formation of OxPC. This supports the view that neutralizing certain OxPL as endogenous activators of TRPA1 or TRPV1 channels may be valuable for pain therapy.