BACKGROUND: Subcutaneous injection of formalin in the plantar surface of rat's hind paw is frequently used as an animal model to study pain associated with inflammation. The pain produced by formalin test differs significantly from that of acute nociceptive tests. In this study, we first investigated the cellular and molecular mechanisms responsible for chronic inflammatory pain-induced damage in the rat hepatocytes and finally we tried to figure out whether both selective (celecoxib) and nonselective (acetylsalicylic acid) cyclo-oxygenase inhibitors could protect hepatocytes against pain-induced damage. METHODS: The male Wistar rats were divided in one-, four-, and seven-day pain groups. Twenty-four hours prior to pain induction with subcutaneous injection of 5% formalin into the hind paw, acetylsalicylic acid or celecoxib was administered to the animals of similar one-, four-, and seven-day pain groups. A no-pain (control) group was also considered for each of the experiments. RESULTS: Our results showed a significant rise in both formation of reactive oxygen species and collapse in the mitochondrial membrane potential (%Delta Psi m) in all pain groups (P<0.05). Significant lysosomal membrane damage and hepatocyte proteolysis were only seen in one-and four-day pain groups (P<0.05). Caspase 3 activity also showed a significant (P<0.05) rise in all three pain groups. CONCLUSION: Formation of reactive oxygen species and mitochondrial/lysosomal damages were significantly inhibited by both acetylsalicylic acid and celecoxib in hepatocytes of all pain- suffering animals. Nonetheless, celecoxib's tendency to raise caspase 3 activities, suggested that it accelerates the apoptosis in hepatocytes of pain-suffering animals. Our results showed that the pain per se, could initiate some harmful signals that affect other cells other than neurons; these malicious signals could be magnified by use of some analgesics particularly selective cyclo-oxygenase inhibitors.
BACKGROUND: Subcutaneous injection of formalin in the plantar surface of rat's hind paw is frequently used as an animal model to study pain associated with inflammation. The pain produced by formalin test differs significantly from that of acute nociceptive tests. In this study, we first investigated the cellular and molecular mechanisms responsible for chronic inflammatory pain-induced damage in the rat hepatocytes and finally we tried to figure out whether both selective (celecoxib) and nonselective (acetylsalicylic acid) cyclo-oxygenase inhibitors could protect hepatocytes against pain-induced damage. METHODS: The male Wistar rats were divided in one-, four-, and seven-day pain groups. Twenty-four hours prior to pain induction with subcutaneous injection of 5% formalin into the hind paw, acetylsalicylic acid or celecoxib was administered to the animals of similar one-, four-, and seven-day pain groups. A no-pain (control) group was also considered for each of the experiments. RESULTS: Our results showed a significant rise in both formation of reactive oxygen species and collapse in the mitochondrial membrane potential (%Delta Psi m) in all pain groups (P<0.05). Significant lysosomal membrane damage and hepatocyte proteolysis were only seen in one-and four-day pain groups (P<0.05). Caspase 3 activity also showed a significant (P<0.05) rise in all three pain groups. CONCLUSION: Formation of reactive oxygen species and mitochondrial/lysosomal damages were significantly inhibited by both acetylsalicylic acid and celecoxib in hepatocytes of all pain- suffering animals. Nonetheless, celecoxib's tendency to raise caspase 3 activities, suggested that it accelerates the apoptosis in hepatocytes of pain-suffering animals. Our results showed that the pain per se, could initiate some harmful signals that affect other cells other than neurons; these malicious signals could be magnified by use of some analgesics particularly selective cyclo-oxygenase inhibitors.
Authors: Ahmad Salimi; Mehrdad Vaghar-Moussavi; Enayatollah Seydi; Jalal Pourahmad Journal: Environ Sci Pollut Res Int Date: 2016-01-22 Impact factor: 4.223
Authors: Elizabeth DE Papathanassoglou; Meropi DA Mpouzika; Margarita Giannakopoulou; Evangelos Bozas; Nicos Middleton; George Tsiaousis; Andreas Karabinis Journal: J Pain Res Date: 2017-01-13 Impact factor: 3.133