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| Author(s): |
Lilian Calili Camargo
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2016-08-29 |
| Examining board members: |
Cláudia Herrera Tambeli;
Andre Schwambach Vieira;
Alexandre Leite Rodrigues de Oliveira;
Celina Monteiro da Cruz Lotufo;
Luana Fischer
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| Advisor: | César Renato Sartori; Cláudia Herrera Tambeli |
| Abstract | |
Epidemiological studies reveal a frequent comorbidity between chronic pain and depression. The treatment of both conditions is still a great challenge for science, and denotes the need for greater understanding of central neuroplasticity mechanisms underlying the development of such states. It has been shown that Brain Derived Neurotrophic Factor (BDNF), promoting neuronal plasticity, participates in the modulation of pain and the etiology of depression. However, it is not known if this neurotrophin in the Nucleus Accumbens (NAc) by protein Tyrosine receptor Kinase B (TrkB) is involved in the process of becoming chronic pain, and if this chronicity would be associated with depression. Since the Ventral Tegmental Area (VTA) is the primary source of BDNF NAc, and that tissue Plasminogen Activator (tPA) is a protease involved in the synthesis of the mature isoform of BDNF from the precursor isoform, was investigated the role of NAc BDNF in the development of persistent hyperalgesia and if this sensitization affects the gene expression of BDNF and tPA in the VTA and the levels of precursor isoforms, truncated and mature BDNF in the NAc. It was also found that the treatment with PGE2 develops depressive-like behavior in animals sensitized. To answer these questions, we used an animal model of persistent hyperalgesia developing that daily administration of Prostaglandin E2 (PGE2) in the rat paw over 14 days, induces nociceptor sensitization state that lasts more than one month. Our data demonstrated that NAc infusion of the selective TrkB antagonist (K252a), during the first seven days of treatment with PGE2, has prevented the development of persistent hyperalgesia. Furthermore, persistent hyperalgesia did not induce depressive behavior in animals, but during the phases of induction (14 days PGE2 administration) and maintenance (14 days after the end of treatment with PGE2), significantly increased gene expression of BDNF and tPA VTA, but not levels of the isoforms of BDNF in the NAc. These results suggest that BDNF in NAc plays a crucial role in the development of persistent hyperalgesia, and therefore, the chronicity of pain (AU) | |
| FAPESP's process: | 12/11371-7 - Role of persistent inflammatory pain in the development of depression-like behavior and in the expression of Brain-derived neurotrophic factor (BDNF) in the Ventral Tegmental Area and Nucleus Accumbens in rats |
| Grantee: | Lilian Calili Camargo |
| Support Opportunities: | Scholarships in Brazil - Doctorate |