Research reportAdministrations of thalidomide into the rostral ventromedial medulla alleviates painful diabetic neuropathy in Zucker diabetic fatty rats

•TNFα, IL-1β, and NFκB is increased in the RVM of ZDF rats.•Thalidomide reduced TNFα, IL-1β, and NFκB in the RVM.•Intra-RVM Thalidomide infusions dose-dependently attenuated diabetic neuropathy.

The rostral ventromedial medulla (RVM) plays a critical role in pain signal transmissions. However, the mechanisms of RVM in type 2 diabetic neuropathy are still poorly understood. Therefore, we evaluated the mechanisms within the RVM in the modulation of neuropathic pain in type 2 diabetes. To this end, we used Zucker diabetic fatty (ZDF) rats to examine the levels of TNFα, IL-1β, and NF-κB in the RVM during the development of neuropathic pain in type 2 diabetes, and evaluated the effects of intra-RVM microinjections of thalidomide on the levels of TNFα, IL-1β, and NF-κB in the RVM and mechanical allodynia and thermal hyperalgesia induced by type 2 diabetes. We found that ZDF rats became hyperglycemic and exhibited increased levels of TNFα, IL-1β, and NFκB in the RVM at the age of 13 weeks. Intra-RVM administrations of thalidomide dose-dependently attenuated mechanical allodynia and thermal hyperalgesia, and this phenomenon was associated with reduced levels of TNFα, IL-1β, and NFκB in the RVM, without altering serum levels of TNFα or IL-1β. These results suggested that supraspinal mechanisms of thalidomide play a critical role in modulations of type 2 diabetes induced neuropathic pain, which is likely mediated by TNFα and IL-1β in the RVM.