Salidroside Ameliorates Diabetic Neuropathic Pain in Rats by Inhibiting Neuroinflammation

More than half of diabetic patients suffer from intractable neuropathic pain. As inflammation plays an important role in diabetic neuropathic pain, anti-inflammatory drugs might have therapeutic potentials for neuropathic pain. Salidroside (SAL), a phenylpropanoid glucoside, modulates a variety of cell functions, including inflammation. Here, we explored anti-nociceptive and anti-inflammatory effects of SAL on Zucker diabetic fatty rats with type 2 diabetes (DM rats). DM rats were tested for mechanical and thermal hyperalgesia using von Frey filament and plantar hot box test, respectively. The anti-nociceptive effect of chronic SAL (25-100 mg/kg, per oral) treatment was tested. The expression of inflammatory cytokines (TNF-α and IL-1β) and P2X₇ receptors in spinal cord and sciatic nerve were measured with ELISA. SAL alleviated mechanical and thermal hyperalgesia and reduced TNF-α and IL-1β in sciatic nerve and spinal cord in DM rats. Furthermore, SAL reduced P2X₇ receptor upregulation in spinal cord of DM rats and directly inhibited P2X₇ receptors expressed in HEK293 cells. This study provides evidence that SAL attenuated nociception in diabetic neuropathic pain rat models probably through inhibiting neuroinflammation and P2X₇ receptors.