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| Author(s): |
Simone Monaliza Silva Lamana
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Piracicaba, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba |
| Defense date: | 2016-07-06 |
| Examining board members: |
Juliana Trindade Clemente Napimoga;
Giovana Tofoli;
Victor Angelo Martins Montalli;
Maria Cristina Volpato;
Patricia Oliveira de Lima
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| Advisor: | Juliana Trindade Clemente Napimoga |
| Abstract | |
Tramadol is a potent drug to treat pain conditions. However, there are no studies supporting the peripheral anti-inflammatory effect of tramadol when administered locally in the temporomandibular joint (TMJ). Thus, the aim of this study was evaluate the peripheral anti-inflammatory effect of tramadol through the induced inflammatory pain in the rats TMJ and elucidate the mechanisms involved. Male Wistar rats were treated with an intra-articular injection of tramadol (125, 250, 500 or 1000 µg/TMJ) co-administrated with 1.5% formalin or capsaicin 1.5%. Animals were pretreated (15 min) with an intra-articular injection of non-selective antagonist of opioid receptors (Naloxone, 10 µg/TMJ); or selective inhibitor of PI3K (AS605240; 30 µg/TMJ); or selective inhibitor of AKT (AKT inhibitor IV; 10 µg/TMJ); or inhibitor of nitric-oxide synthase (L-NMMA; 450 µg/TMJ); or inhibitor of soluble cGMP enzyme (ODQ; 80 µg/TMJ); or inhibitor of PKG (KT5823; 1.5 µg/TMJ); or the ATPpotassium sensitive channel blocker (Glibenclamide; 160 µg/TMJ) followed of an intra-articular injection of tramadol (500 µg/TMJ) with 1.5% formalin. In another set of experiments, the animals were pretreated (15 min) with an intra-TMJ injection of tramadol (125, 250 and 500 µg/TMJ) followed by: (1) an intra-TMJ injection of carrageenan (100 µg/TMJ) 1 hour prior an intra-articular injection of a low dose of 5-hidroxytryptamine (5-HT, 75µg/TMJ) or (2) an intra-articular injection of 5-HT (225 µg/TMJ). After TMJ treatments, the behavioral nociception responses were evaluated then the animals were euthanized and the periarticular tissues removed for analysis. The intra-articular injection of tramadol 250, 500 and 1000 but not 125 µg/TMJ significantly reduced behavioral nociceptive responses induced by 1.5% formalin (P<0.05). The contralateral intra-articular injection of tramadol (1000 µg/TMJ) did not affect the 1.5% formalin-induced behavioral nociceptive responses (P>0.05) confirming the peripheral effect of tramadol. The intra-articular injection of tramadol (500 mg/TMJ) significantly reduced the capsaicin-induced behavioral nociceptive responses (P<0.05) suggesting that tramadol has a direct effect on nociceptive C-fibers. The pretreatment with L-NMMA and ODQ but not naloxone, AS605240, AKT inhibitor IV, KT5823 and glibenclamide significantly reduced the peripheral antinociceptive effect induced by intra-articular injection of tramadol (500 µg/TMJ) (P<0.05). These results suggest that tramadol depends on the activation of intracellular NO/cGMP pathway independently of opioid receptors. The pretreatment with Tramadol 500 but not 250 and 125 µg/TMJ significantly reduced behavioral nociceptive responses induced by carrageenan or 5-HT (P<0.05). The intra-articular injection of tramadol (500 µg/TMJ) did not affect the expression of ICAM and CD55 (P>0.05) but significantly reduced the release of inflammatory cytokines TNF-? and IL-1? induced by 1.5% formalin or carrageenan (P<0.05). The pretreatment with tramadol (125, 250 and 500 µg/TMJ) significantly reduced carrageenan-induced leukocytes migration and plasma extravasation (P<0.05). The results suggest that tramadol has a potential anti-inflammatory effect by reducing the inflammatory chemotaxis thought intracellular activation of the NO/cGMP pathway (AU) | |
| FAPESP's process: | 13/11090-0 - ASSESSMENT OF ANTI-INFLAMMATORY EFFECT OF PERIPHERAL TRAMADOL IN THE TEMPOROMANDIBULAR JOINT IN RATS. |
| Grantee: | Simone Monaliza Silva Lamana |
| Support Opportunities: | Scholarships in Brazil - Doctorate |