Effect of hemopressin - an inverse agonist of cannabinoid receptors type 1 - in diabetes mellitus-induced neuropathy in mice

Abstract

The peripheral neuropathy caused by diabetes mellitus is the most common complication of diabetes, affecting around 50% of patients with this illness. One of the most prominent symptoms of this neuropathy is the development of pain that involves the extremities and occurs as both an exaggerated response to noxious stimuli (hyperalgesia) and for light or non-painful stimuli (allodynia). Cellular mechanisms involved in diabetic pain involve multiple factors and are poorly understood. Thus, the treatment of neuropathic pain in diabetes is inadequate and unsatisfactory. The use of cannabinoid receptors-based compounds appears as a new therapeutic option since. Data obtained by our group demonstrates that hemopressin, an inverse agonist of CB1 receptors inhibits nociceptive response in rats with neuropathic pain. This project aims to identify the therapeutic potential of hemopressin on the neuropathic pain induced by streptozotocin in mice. The effect of hemopressin on pain sensitivity of animals will be evaluated on in vivo models for assessing pain sensitivity. For an understanding of the possible mechanisms involved in pain inhibition histological and biochemical parameters of neuronal regeneration will be evaluated. The activation of glial cells and the expression of CB1 receptors will be performed in vitro assays of immunohístochemistry, immunoblotting and ELISA in slice, which will signal the levei of protein synthesis as well as the possible receptors involved, providing data of the local effects and the distant circuits of the hemopressin effect. The results will allow a better understanding of the effectiveness of a peptide acting directly on CB1 receptors, providing additional tools for understanding the modulation of the endocannabinoid system, as well as the discovery of new therapeutic strategies effective in treating diseases involving cannabinoid receptors. (AU)