Minocycline attenuates the development of diabetic neuropathy by modulating DREAM and BDNF protein expression in rat spinal cord

Abstract

Aim: This study investigates the effects of minocycline (an inhibitor of microglial activation) administration on the expression level of spinal BDNF and DREAM proteins in diabetic neuropathic pain (DNP) rats. Methods: The rats were divided into four groups (n = 16): non-diabetic control, diabetic control and diabetic rats receiving minocycline (80 μg/day or 160 μg/day). The diabetic rat model was induced by intraperitoneal injection of streptozotocin (60 mg/kg STZ). Tactile allodynia was assessed on day-0 (baseline), day-14 (pre-intervention) and day-22 (post-intervention). Minocycline at doses of 80 μg and 160 μg were given intrathecally from day-15 until day-21. On day-23, formalin test was conducted to assess nociceptive behaviour response. The spinal expression of OX-42 and level of BDNF and DREAM proteins were detected by immunohistochemistry and western blot analyses. Results: Diabetes rats showed significant tactile allodynia and nociceptive behaviour. These were accompanied by augmented expression of spinal OX-42, BDNF and DREAM protein levels. Both doses of minocycline attenuated tactile allodynia and nociceptive behaviour and also suppressed the diabetic-induced increase in spinal expressions of OX-42, BDNF and DREAM proteins. Conclusion: This study revealed that minocycline could attenuate DNP by modulating spinal BDNF and DREAM protein expressions.