Hemopressin an Inverse Agonist of Cb1 Cannabinoid Receptors Reverses Mechanical Sensitivity on Diabetes-Induced Neuropathy in Mice

Peripheral neuropathy is one of the most common complications of diabetes affecting about 50% of patients with the disease. The most prominent symptoms involve the extremities and occur as both an exaggerated response to noxious stimuli (hyperalgesia), mild or non-painful stimuli (allodynia). Hemopressin (Hp) is a non apeptide first found in rat brain extracts, which selectively binds CB1 cannabinoid receptors (CB1R) and exerts antinociceptive actions in experimental inflammatory and neuropathic pain models. However there is no data about its efficacy in neuropathic metabolic-related disease, like diabetes mellitus. The aim of this study was to investigate the role of Hp on mechanical and thermal sensitivity of mice submitted to an experimental model of type 1 diabetes mellitus-induced neuropathy. Mechanical allodynia and thermal sensibility were assessed by von Frey filaments or plantar test, respectively, 7, 14, 21 and 28 days after streptozotocine injection (STZ; 200 mg/kg). Body weight and blood glucose were monitored once a week. Hp was administered orally, once a day (2.5 mg/kg) for 28 days. Hp reversed mechanical allodynia in diabetic mice without changing blood glucose levels or body weight. No effects were observed for thermal sensitivity. These results make hemopressin an attractive approach for the development of cannabinoid-based therapies for the treatment diabetic neuropathic pain.