PT  - JOURNAL ARTICLE
AU  - Guilherme Carneiro Montes
AU  - Nathalia Hammes
AU  - Miguel Divino da Rocha
AU  - Tadeu Lima Montagnoli
AU  - Carlos Alberto Manssour Fraga
AU  - Eliezer J. Barreiro
AU  - Roberto Takashi Sudo
AU  - Gisele Zapata-Sudo
TI  - Treatment with Adenosine Receptor Agonist Ameliorates Pain Induced by Acute and Chronic Inflammation
AID  - 10.1124/jpet.115.231241
DP  - 2016 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 315--323
VI  - 358
IP  - 2
4099  - http://jpet.aspetjournals.org/content/358/2/315.short
4100  - http://jpet.aspetjournals.org/content/358/2/315.full
SO  - J Pharmacol Exp Ther2016 Aug 01; 358
AB  - 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 inducible nitric oxide synthase (iNOS) expression as well as histologic features were analyzed. The time of reactivity to formalin in the neurogenic phase was reduced from 56.3 ± 6.0 seconds to 32.7 ± 2.2 seconds and 23.8 ± 2.6 seconds after 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 the inflammatory phase after treatment with ZM 241385 [4-(2-[7-amino-2-(2-furly)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol], 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 after 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 histologic analysis. These results suggest that LASSBio-1359 represents an alternative treatment of monoarthritis.