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Cyclo‐Gly‐Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice
Author(s) -
Ferro Jamylle Nunes de Souza,
Aquino Fernanda Lima Torres,
Brito Renan Guedes,
Santos Priscila Laíse,
Quintans Jullyana de Souza Siqueira,
Souza Lucas Costa,
Araújo Almair Ferreira,
Diaz Bruno Lourenço,
LuccaJúnior Waldecy,
QuintansJúnior Lucindo José,
Barreto Emiliano
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12480
Subject(s) - carrageenan , nociception , chemistry , pharmacology , periaqueductal gray , hyperalgesia , (+) naloxone , hot plate test , intraperitoneal injection , medicine , biochemistry , opioid , central nervous system , endocrinology , receptor , midbrain
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 E 2 ( PGE 2 ) 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 PGE 2 . 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.