Research of the effects of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) on pain and inflammation

Research of the Effects of Glucagon-Like Peptide-1 (GLP-1) and Glucagon-Like Peptide-2 (GLP-2) on Pain and Inflammation Introduction: The aim of this study is to investigate the effects of GLP-1 and GLP-2 on nociception and inflammation in mice with hot plate and formalin tests. Methods: The effects and mechanisms of GLP-1 and GLP-2 were evaluated in acute and chronic administration, in hot plate and formalin tests. Rotarod test and blood glucose measurement were performed to check whether locomotor activity and blood glucose level contributed to these effects. Results: GLP-1 and GLP-2 showed statistically significant increases in antinociceptive effects compared to saline at 0.2 mg/kg doses at 30. min. Significant change was observed in nociception at 10. min with GLP-1 0.05 mg/kg. Paw licking and shaking numbers of GLP-1 0.2 mg/kg, GLP-2 0,2 mg/kg and GLP-2 0,1 mg/kg at acute and tonic phases (except the paw licking after GLP-2 0.1 mg/kg dosage at acute phase), paw shaking number of GLP-1 0.1 mg/kg at tonic phase, and paw shaking number of GLP-2 0.05 mg/kg at acute and tonic phases were significantly decreased. The antinociceptive effects of GLP-1 in the presence of L-NAME at 15. min and in the presence of ondansetron, L-NAME and nalokson at 30. min, GLP-2 in the presence of ondansetron and nalokson at 30. min were significantly decreased. In GLP-2, paw licking numbers at acute and tonic phases, and paw shaking numbers at tonic phase with L-NAME, paw shaking numbers at tonic phase with ondansetron were significantly decreased while significant increase in paw shaking numbers at acute phase only with naloxon were seen at GLP-1. The antinociceptive effects of GLP-1 0.2 mg/kg and GLP-2 0.05 mg/kg after chronically administration were significantly increased at 10., 15., and 30. min compared to saline, while paw movement numbers (except paw shaking after GLP-2 at tonic phase) were significantly decreased at all time intervals compared to saline. The effects of GLP-1 and GLP-2 on locomotor activity and blood glucose levels did not alter antinociceptive and antiinflammatory activities. Conclusion and Results: In this study, we found antinociceptive and antiinflammatory effects of GLP-1 and GLP-2, and different results about serotonergic, nitrergic and opioidergic pathways. As a further study, we aim to investigate PKA-dependent protein expression at the molecular level to clarify the results we have found. Key Words: GLP-1, GLP-2, pain, inflammation.