Investigação das implicações fisiopatológicas da via das quinureninas na dor neuropática diabética

Abstract

The global prevalence of diabetes reached 9.3% of the world population, with type 2 diabetes being responsible for about 90% of all cases. Among the possible complications arising from diabetes, we can highlight diabetic neuropathy. In recent decades, activation of the enzyme indoleamine-2,3-dioxygenase (IDO-1) has been reported, promoting the formation of active metabolites known as kynurenines. These bioactive metabolites activate specific receptors that support inflammatory and neuropathic pain. It is also known that this metabolic pathway substantially reduces the levels of the neurotransmitter serotonin (5HT), corroborating to the pain and

depression. Therefore, the aim of this work was investigate the participation of the IDO- 1 enzyme in the induction and maintenance of neuropathic pain induced by diabetes

in rats and its relationship with depression in humans. Experimental diabetes was induced by intraperitoneal administration of alloxan (150mg/kg). Allodynia was evaluated using von Frey filaments before and after pharmacological inhibition of the IDO-1 enzyme in diabetic rats. Looking to find comorbidities in diabetes, patients from the Family Health Program of the city of Patos de Minas - MG were selected. Peripheral blood was collected to measure glycohemoglobin and serotonin in serum. The levels of the serotonin metabolite 5-HIAA in the patients' urine were also quantified. Our results in animals demonstrated that diabetic rats treated with IDO-1 enzyme inhibitor showed reduced allodynia. The results obtained in diabetic patients demonstrate lower plasma levels of serotonin and higher levels of 5-HIAA. Furthermore, we evaluated the medical records of neuropathic diabetic patients and found that some patients also had depressive comorbidity. Thus, we can suggest the involvement of the IDO-1 enzyme in diabetes-induced neuropathic pain and a possible depressive comorbidity in these evaluated patients.