ABSTRACT
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-1ß) 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-1ß 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.
Subject(s)
Analgesics/therapeutic use , Diabetic Neuropathies/drug therapy , Glucosides/therapeutic use , Nociception , Phenols/therapeutic use , Analgesics/pharmacology , Animals , Diabetic Neuropathies/metabolism , Glucosides/pharmacology , HEK293 Cells , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Phenols/pharmacology , Rats , Rats, Zucker , Receptors, Purinergic P2X7/genetics , Receptors, Purinergic P2X7/metabolism , Sciatic Nerve/drug effects , Sciatic Nerve/metabolism , Spinal Cord/drug effects , Spinal Cord/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder, characterized by intense fear, and increased arousal and avoidance of traumatic events. The current available treatments for PTSD have limited therapeutic value. Genistein, a natural isoflavone, modulates a variety of cell functions. In this study, we tested anti-anxiety activity and underlying mechanisms of genistein in a PTSD rat model. The rats were trained to associate a tone with foot shock delivery on day 0, then fear conditioning was performed on day 7, 14 and 21. Genistein (2-8mg/kg) was injected intraperitoneally daily for 7 days. The anti-anxiety effects of genistein were measured by contextual freezing behavior and elevated plus maze. By the end of the experiments, the amygdala was extracted and subject to neurochemistry analysis. Genistein alleviated contextual freezing behavior and improved performance in elevated plus maze dose-dependently in PTSD rats. Furthermore, in these rats, genistein enhanced serotonergic transmission in the amygdala, including upregulation of tryptophan hydroxylase, serotonin, and phosphorylated (p)-CaMKII and p-CREB, as well. Genistein exerts anti-anxiety effects on a PTSD model probably through enhancing serotonergic system and CaMKII/CREB signaling pathway in the amygdala.
