Role of indoleamine 2,3-dioxygenase in the induction and maintenance of neuropathic pain

• Grant number: 11/13097-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2011
• End date: October 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Guilherme Rabelo de Souza
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis, AP.TEM
• Associated scholarship(s): 13/00439-2 - Role of indoleamine 2,3-dioxygenase in the induction and maintenance of neuropathic pain, BE.EP.PD

Abstract

Abstract Chronic pain is one of the most important health problem of our society. Among pain types, the neuropathic pain stills a challenge for the researchers of pain and physicians, since there are no effective treatments. Tricyclic antidepressant drugs are widely used in the management of psychological disorders and various types of pain, including neuropathic pain, suggesting the involvement of descending monoaminergic pain modulation. This endogenous system that control nociceptive information seem to be suppressed in chronic pain. However, the mechanisms involved in the negative regulation are not understood. One factor that might be involved in the down-modulation of the descending control during neuropathic pain would be the increased degradation of the essential amino acid for the serotonin synthesis - the triptophan (Trp) by the activation of the indoleamine 2,3-dioxygenase (IDO). IDO could also cause an increase in serotonin degradation. It has been demonstrated that pro-inflammatory cytokines such as INF±/³, TNF-± and IL-6 and intracellular signaling pathways such as MAPK (p38, ERK and JNK) and NF-ºB play a role in the expression and activity of enzyme IDO in different cell types. After peripheral nerve injuries there are an increase in the expression and activity of these factors in the spinal cord. Therefore, it is likely that they could increase the expression of IDO in the spinal cord. In this context, the main aim of the project is evaluate the participation of IDO in the induction and maintenance of neuropathic pain and the possible mechanisms involved in its induction. We believe these study will open a avenue in the development of new drugs for the treatment of neuropathic.