title: Involvement of mast cells in a mouse model of postoperative pain.
abstract: Recent studies have indicated that nearly half of all surgical patients still have inadequate pain relief; therefore, it is becoming increasingly more important to understand the mechanisms involved in postoperative pain in order to be better treated. Previous studies have shown that incisions can cause mast cell degranulation. Thus, the aim of this study was to investigate the involvement of mast cells in a model of postoperative pain in mice. The depletion of mast cell mediators produced by pre-treatment with compound 48/80 (intraplantar (i.pl.)) widely (98 ± 23% of inhibition) and extensively (up to 96 h) prevented postoperative nociception and reduced histamine and serotonin levels (88 ± 4% and 68 ± 10%, respectively) in operated tissue. Furthermore, plantar surgery produced immense mast cell degranulation, as assessed by histology and confirmed by the increased levels of serotonin (three-fold higher) and histamine (fifteen-fold higher) in the perfused tissue, 1h after surgery. Accordingly, pre-treatment with the mast cell membrane stabilizer cromoglycate (200 μg/paw, i.pl.) prevented mechanical allodynia (inhibition of 96 ± 21%) and an increase in histamine (44 ± 10% of inhibition) and serotonin (73 ± 5% of inhibition) levels induced by plantar surgery. Finally, local treatment with H(1) (promethazine, 100 μg/paw, i.pl.), 5-HT(3) (ondansetron, 10 μg/paw, i.pl.) or 5-HT(2A) (ketanserin, 5 μg/paw, i.pl.) receptor antagonists partially decreased postoperative nociception in mice, but when co-administered together it completely reversed the mechanical allodynia in operated mice. Thus, mast cell activation mechanisms are interesting targets for the development of novel therapies to treat postoperative pain.
authors: Programa de Pós-graduação em Ciências Biológicas, Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors: Sara Marchesan
authors: SM
authors: Oliveira
authors: Carine Cristiane
authors: CC
authors: Drewes
authors: Cássia Regina
authors: CR
authors: Silva
authors: Gabriela
authors: G
authors: Trevisan
authors: Suelen Lucio
authors: SL
authors: Boschen
authors: Camila Guimaraes
authors: CG
authors: Moreira
authors: Daniela
authors: D
authors: de Almeida Cabrini
authors: Claudio
authors: C
authors: Da Cunha
authors: Juliano
authors: J
authors: Ferreira
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D004195:Disease Models, Animal; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D059225:Nociception / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000523:psychology; D011969:Receptors, Histamine H1 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D012701:Serotonin; D006632:Histamine