The antihyperalgesic and antiallodynic effects of reboxetine in streptozotocin induced diabetic rats and investigating the underlying mechanisms using pharmacological and morphometric methods

In this study, the effects of reboxetine, a potent and selective noradrenaline reuptake inhibitor, were investigated on the plasma glucose levels and hyperalgesia and allodynia responses of diabetic rats with experimental diabetes. Reboxetine administations for 7 and 14 days (8 and 16 mg.kg-1) did not cause any significant change in the plasma glucose levels of diabetic rats. The results of Randall-Selitto (mechanical hyperalgesia), dynamic plantar (mechanical allodynia), Hargreaves (thermal hyperalgesia) and warm plate (thermal allodynia) tests, performed to evaluate neuropathic pain, showed that reboxetine treatment improves diabetes-induced hyperalgesia and allodynia responses, which was comparable to reference drug pregabalin. Treatments of animals with phentolamine, metoprolol, SR 5923A and atropine for clarifying the underlying mechanisms did not alter; while a-methyl-para-tyrosine methyl ester, propranolol, ICI 118,551, SCH 23390, sulpiride and naltrindol pretreatments significantly reversed the presented effects of reboxetine. These findings pointed out that the antihyperalgesic and antiallodynic effects of reboxetine were mediated by the participation of catecholaminergic system, β2-adrenoceptors, D1, D2/D3-dopaminergic receptors and δ-opioid receptors. On the other hand, reboxetine administration did not cause a significant difference in the morphology of dorsal root ganglion neurons in diabetic rats. These preclinical findings of this study indicate that this drug has a great potential in the treatment of diabetes-induced neuropathic pain. Keywords: Allodynia, Dorsal root ganglion, Hyperalgesia, Reboxetine