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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pavao-de-Souza, Gabriela F. Zarpelon, Ana C. Tedeschi, Giovana C. Mizokami, Sandra S. Sanson, Joice S. Cunha, Thiago M. Ferreira, Sérgio H. Cunha, Fernando Q. Casagrande, Rubia Verri, Waldiceu A. |
| Description | Country affiliation: Brazil Author Affiliation: Pavao-de-Souza GF ( Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil.) |
| Abstract | The acetic acid and phenyl-p-benzoquinone are easy and fast screening models to access the activity of novel candidates as analgesic drugs and their mechanisms. These models induce a characteristic and quantifiable overt pain-like behavior described as writhing response or abdominal contortions. The knowledge of the mechanisms involved in the chosen model is a crucial step forward demonstrating the mechanisms that the candidate drug would inhibit because the mechanisms triggered in that model will be addressed. Herein, it was investigated the role of spinal mitogen-activated protein (MAP) kinases ERK (extracellular signal-regulated kinase), JNK (Jun N-terminal Kinase) and p38, PI(3)K (phosphatidylinositol 3-kinase) and microglia in the writhing response induced by acetic acid and phenyl-p-benzoquinone, and flinch induced by formalin in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing response over 20 min. The nociceptive response in these models were significantly and in a dose-dependent manner reduced by intrathecal pre-treatment with ERK (PD98059), JNK (SB600125), p38 (SB202190) or PI(3)K (wortmannin) inhibitors. Furthermore, the co-treatment with MAP kinase and PI(3)K inhibitors, at doses that were ineffective as single treatment, significantly inhibited acetic acid- and phenyl-p-benzoquinone-induced nociception. The treatment with microglia inhibitors minocycline and fluorocitrate also diminished the nociceptive response. Similar results were obtained in the formalin test. Concluding, MAP kinases and PI(3)K are important spinal signaling kinases in acetic acid and phenyl-p-benzoquinone models of overt pain-like behavior and there is also activation of spinal microglia indicating that it is also important to determine whether drugs tested in these models also modulate such spinal mechanisms. |
| File Format | HTM / HTML |
| ISSN | 00913057 |
| Issue Number | 3 |
| Volume Number | 101 |
| e-ISSN | 18735177 |
| Journal | Pharmacology Biochemistry and Behavior |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-05-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Behavioral Sciences Discipline Biochemistry Discipline Pharmacology Acetic Acid Toxicity Benzoquinones Pain Chemically Induced Physiopathology Androstadienes Pharmacology Animals Anthracenes Disease Models, Animal Flavonoids Imidazoles Injections, Spinal Map Kinase Signaling System Drug Effects Male Mice Microglia Physiology Nociception Nociceptive Pain Pain Measurement Phosphatidylinositol 3-kinases Antagonists & Inhibitors Pyridines Spinal Cord Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biological Psychiatry Behavioral Neuroscience Biochemistry Clinical Biochemistry Toxicology Pharmacology |
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