Abstract
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.
Highlights
Treatment with Hp does not interfere with thermal sensitivity of diabetic mice Mice treated with streptozotocine injection (STZ) (n=5) showed a loss on pain sensitivityto the thermal stimulation in all evaluated times when compared with Sal+ Sal group (n=5) (Figure 2)
Results presented demonstrate that STZ-induced diabetic mice showed a decrease on mechanical pain threshold when compared to non-diabetic mice, in all evaluated times
This result is consistent with previous reports from literature demonstrating that diabetic mice show a low pain threshold, characterizing the diabetic neuropathy as a model of neuropathic pain [21]
Summary
Diabetic peripheral neuropathy (DPN) caused by diabetes mellitus is one of the most common complications of diabetes affecting about 50% of patients with the disease [1,2]. Among the many symptoms of this neuropathy, the development of chronic pain is one of the major complications on ceits emergence depends on multifactorial components, which are still poorly understood [3]. This neuropathic pain typically involves the extremities and is characterized by spontaneous and evoked pain stimuli with changes in pain perception, increased sensitivity to noxious stimuli (hyperalgesia) and sensitivity to light stimuli or stimuli that previously were not painful (allodynia). An alternative therapy that has gained clinical acceptance is the use of compounds that modulate cannabinoid receptors, once these receptors are expressed in both neurons and microglia of rats with diabetic neuropathy, at both spinal and supraspinall evels [11,14,15,16]
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