Cyclo-Gly-Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice

• Published in: Clinical and experimental pharmacology & physiology Vol. 42; no. 12; pp. 1287 - 1295
• Main Authors: Ferro, Jamylle Nunes de Souza, de Aquino, Fernanda Lima Torres, de Brito, Renan Guedes, dos Santos, Priscila Laíse, Quintans, Jullyana de Souza Siqueira, de Souza, Lucas Costa, de Araújo, Almair Ferreira, Diaz, Bruno Lourenço, Lucca-Júnior, Waldecy, Quintans-Júnior, Lucindo José, Barreto, Emiliano
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01-12-2015; Wiley Subscription Services, Inc
• Subjects: Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; anti-inflammatory effect; antinociceptive effect; Behavior, Animal - drug effects; cyclic dipeptide; Gene Expression Regulation - drug effects; Hyperalgesia - drug therapy; inflammation; Inflammation - drug therapy; Male; Mice; Nociception - drug effects; opioid receptor; Peptides, Cyclic - pharmacology; Peptides, Cyclic - therapeutic use; periaqueductal gray; Periaqueductal Gray - drug effects; Periaqueductal Gray - metabolism; Proto-Oncogene Proteins c-fos - metabolism; Rotarod Performance Test; opioid receptor; antinociceptive effect; anti-inflammatory effect; cyclic dipeptide; inflammation; periaqueductal gray
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12480

Summary
The present study aimed to investigate the antinociceptive and anti‐inflammatory effects of the cyclic dipeptide cyclo‐Gly‐Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid‐induced writhing, hot plate test, and carrageenan‐induced hyperalgesia, in mice. The number of c‐Fos‐immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP‐treated mice. Anti‐inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin‐induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid‐induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP‐treated mice there was an increase in the number of c‐Fos‐positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan‐increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2. Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo‐Gly‐Pro toward alleviating nociception and damage caused by inflammation conditions.