Effects of histamine H3 receptors on chemical hyperalgesia in diabetic rats

There is considerable interest in histamine H3 receptors as emerging pharmaceutical targets recently. Diabetic rats display increased pain responses following the injection of formalin into the paw suggesting the presence of hyperalgesia. In this study, the efficacy of systemic administration of selective H3 receptor agonist, immepip (1, 5 and 30 mg/kg), and antagonist, thioperamide (5, 15 and 30 mg/kg), was investigated on hyperalgesia during the formalin test in streptozocin (STZ)-induced diabetic rats. Nociceptive testing was performed in male adult Wistar rats 4 weeks after the onset of hyperglycemia. At the end of the experiment, all rats were weighed and then underwent plasma glucose measurement. Diabetes caused significant hyperalgesia during both phases of the formalin test. 5 and 30 mg/kg doses of immepip reversed chemical hyperalgesia in diabetic rats. The 1 mg dose of immepip did not alter pain behaviors in control and diabetic groups compared to the respective control ones. Immepip at any doses used in this study did not affect the body weight and plasma glucose levels of treated animals. Thioperamide alone at any doses used had no effect on formalin-induced nociceptive behaviors in the control and diabetic rats.The results indicated the efficacy of immepip systemic administration in an experimental model of diabetic hyperalgesia. It may also suggest it as a promising tool for treatment of painful diabetic neuropathy.

► The efficacy of H3 receptor agonist, immepip and antagonist, thioperamide was investigated on hyperalgesia during the formalin test in streptozocin-induced diabetic rats.
► Iimmepip reversed chemical hyperalgesia in diabetic rats.
► Immepip did not affect the body weight and plasma glucose levels of treated animals.
► Thioperamide showed no efficacy in this model of diabetic hyperalgesia.