Cyclo-Gly-Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice.
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.
Laboratory of Cell Biology, Federal University of Alagoas, Maceió, Brazil.
Jamylle Nunes de Souza
JN
Ferro
Laboratory of Cell Biology, Federal University of Alagoas, Maceió, Brazil.
Fernanda Lima Torres
FL
de Aquino
Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
Renan Guedes
RG
de Brito
Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
Priscila Laíse
PL
dos Santos
Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
Jullyana de Souza Siqueira
Jde S
Quintans
Laboratory of Inflammation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Lucas Costa
LC
de Souza
Laboratory of Inflammation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Almair Ferreira
AF
de Araújo
Laboratory of Inflammation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Bruno Lourenço
BL
Diaz
Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
Waldecy
W
Lucca-Júnior
Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil.
Lucindo José
LJ
Quintans-Júnior
Laboratory of Cell Biology, Federal University of Alagoas, Maceió, Brazil.
Emiliano
E
Barreto
D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D059225:Nociception / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D045442:Rotarod Performance Test
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010456:Peptides, Cyclic; D016760:Proto-Oncogene Proteins c-fos; C016325:cyclo(glycylprolyl)
anti-inflammatory effect; antinociceptive effect; cyclic dipeptide; inflammation; opioid receptor; periaqueductal gray