Rheumatoid arthritis is an inflammatory autoimmune condition and tumor necrosis factor-α (TNF-α) plays an important role in its pathophysiology. In vitro, (E)-N'-(3,4-dimethoxybenzylidene)-N-methylbenzohydrazide (LASSBio-1359) has exhibited anti-TNF-α properties and in vivo these effects are mediated via activation of adenosine receptor. This work investigates the antinociceptive action of LASSBio-1359 in murine models of acute and chronic inflammatory pain. Male mice received an intraperitoneal injection of LASSBio-1359 and then were evaluated in formalin- and carrageenan-induced paw edema assays. Complete Freund's Adjuvant (CFA) was used to induce a mouse model of monoarthritis. These mice were treated with LASSBio-1359 by oral gavage to evaluate thermal and mechanical hyperalgesia. TNF-α and i-NOS expression, as well as histological features were also analyzed. The time of reactivity to formalin in the neurogenic phase was reduced from 56.3 ± 6.0 s to 32.7 ± 2.2 s and 23.8 ± 2.6 s following treatment with LASSBio-1359 at doses of 10 mg/kg and 20 mg/kg, respectively. A reversal of the antinociceptive action of LASSBio-1359 was observed in inflammatory phase following treatment with ZM 241385, an adenosine A2A antagonist. Carrageenan-induced thermal and mechanical hyperalgesia were reduced after treatment with LASSBio-1359. Similarly, CFA-induced thermal and mechanical hyperalgesia were reduced following treatment with LASSBio-1359 (25 and 50 mg/kg). Levels of TNF-α and iNOS expression increased in the monoarthritis model and were normalized in animals treated with LASSBio-1359 which was also associated with beneficial effects in the histological analysis. These results suggest that LASSBio-1359 represents an alternative treatment for monoarthritis.
- The American Society for Pharmacology and Experimental Therapeutics