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

Abstract

Chronic pain is one of the most common problems of our society. Among pain types, the neuropathic pain still is 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 controls nociceptive information seems 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. Furthermore, there is evidence that metabolites derived from IDO activity show neuro-excitatory effects through NMDA signaling, an important component of chronic pain development. 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 that in turn might cause a dysregulation of descending endogenous monoaminergic pain pathway. In this context, the main aim of the project is evaluate the participation of IDO in neuropathic pain and the possible mechanisms involved in its induction. We believe these study will open an avenue in the development of new drugs for the treatment of neuropathic pain. (AU)