Conclusions
The NE inhibitor EL-17 relieved articular pain after acute administration. Furthermore, repeated treatment reduced the development of hypersensitivity and protected joint tissue, revealing a disease-modifying profile.
Methods
Complete Freund's Adjuvant (CFA) was injected in the tibiotarsal joint and the effect of acute or repeated treatments with EL-17 (1-30 mg/kg by mouth) were evaluated.
Results
On day 14 after CFA injection, a single administration of EL-17 significantly reduced CFA-dependent hypersensitivity to mechanical noxious stimuli and the postural unbalance related to spontaneous pain. To evaluate the preventive efficacy, EL-17 was administered daily starting from the day of CFA treatment. Behavioural measurements performed on days 7 and 14 showed a progressive efficacy of EL-17 against hypersensitivity to mechanical noxious and non-noxious stimuli, as well as a decrease of hind limb weight-bearing alterations. Histological evaluation of the tibiotarsal joint (day 14) demonstrated significant prevention of articular derangement after EL-17 (30 mg/kg) treatment. The protective effects of EL-17 directly correlated with a complete reversion of the plasma NE activity increase induced by CFA. Conclusions: The NE inhibitor EL-17 relieved articular pain after acute administration. Furthermore, repeated treatment reduced the development of hypersensitivity and protected joint tissue, revealing a disease-modifying profile.