Antinociception induced by a novel α2A adrenergic receptor agonist in rodents acute and chronic pain models

• Published in: European journal of pharmacology 2017-11, Vol.815, p.210-218
• Main Authors: Sudo, Roberto Takashi, do Amaral, Rachel Vieiralves, Monteiro, Carlos Eduardo da Silva, Pitta, Ivan da Rocha, Lima, Maria do Carmo, Montes, Guilherme Carneiro, Ririe, Douglas Gordon, Hayashida, Kenichiro, Zapata-Sudo, Gisele
• Format: Article
• Language: English
• Subjects: Acute and chronic pain; Clonidine; Locus coeruleus; PT-31; α2A adrenoceptors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2017.09.018

The mechanisms and antinociceptive effects of a novel α2A adrenoceptor agonist, 3-(2-chloro-6-fluorobenzil)-imidazolinide-2,4-dione (PT-31) were investigated using animal models of acute and chronic pain. The effects of PT-31 on pain responses were examined using hot plate and formalin tests in mice and spinal nerve ligation (SNL)-induced hyperalgesia in rats. The effects of antagonists acting on α adrenoceptor were assessed to investigate the interaction of these pathways upon PT-31 induced antinociception. PT-31 effects on motor activity/skills and on hemodynamic parameters were also evaluated. PT-31 had dose-dependent antinociception effects on hot-plate and formalin-injection induced pain responses. Thermal hyperalgesia and mechanical allodynia were reduced following a 7 d treatment with PT-31 (1, 5, and 10mg/kg/d, p.o.), and those effects were attenuated by yohimbine (5mg/kg), atropine (2mg/kg), L-nitro arginine methyl ester (L-NAME; 30mg/kg), or naloxone (2mg/kg). In contrast to clonidine, PT-31 did not have locomotor or hemodynamic effects in rats. The present results suggest that PT-31 represents a candidate for pain treatment with advantages over clonidine, namely no locomotor or hemodynamic impairments.