Abstract
Diabetic neuropathic pain (DNP) and major depressive disorder (MDD) are common complications of diabetes mellitus and mutually affect each other. As a member of the ATP-gated ion channel family, P2X7 receptor is associated with the transduction of pain signal and the onset of depression. The aim of this study was to investigate the effects of dihydromyricetin (DHM) on rats with comorbid DNP and MDD. After the comorbid model was established, rat behavior changes were monitored by measuring the mechanical withdrawal threshold, thermal withdrawal latency, sugar water preference, immobility time in the forced-swim test, and open-field test parameters. The expressions of P2X7 receptor in the dorsal root ganglia (DRGs), spinal cord, and hippocampus were assessed by quantitative real-time PCR, Western blotting, and double immunofluorescence. We found that hyperalgesia, allodynia, and depressive behaviors of rats with comorbid DNP and MDD were relieved by treatment with DHM or application of a short-hairpin RNA for P2X7 receptor. The expression levels of P2X7, phosphorylated extracellular signal–regulated kinase 1/2, tumor necrosis factor α, and interleukin 1ß were increased in the DRGs, spinal cord, and hippocampus of rats in the model group but restored after DHM or P2X7 short-hairpin RNA treatment. In conclusion, P2X7 receptor in the DRGs, spinal cord, and hippocampus participates in the transduction of DNP and MDD signals. DHM seems to relieve comorbid DNP and MDD by reducing the expression of P2X7 receptor in the DRGs, spinal cord, and hippocampus and may be an effective new drug for the treatment of patients with both DNP and MDD.
Highlights
Given the high prevalence of diabetes mellitus worldwide, diabetic neuropathic pain (DNP) has become a relatively common condition [1, 2]
Two weeks after injection of DHM or 1 week after injection of P2X7 short-hairpin RNA (shRNA), the Mechanical withdrawal threshold (MWT) and Thermal withdrawal latency (TWL) were significantly lower in the model + P2X7 shRNA and model + DHM groups than in the model group (p < 0.05), indicating that both P2X7 shRNA and DHM treatment relieve neuropathic pain– related behavior in rats with Diabetic neuropathic pain (DNP) and major depressive disorder (MDD) (Figures 2A, B)
Our analysis of sucrose preference (SP) in the respective test and of the distance traveled in the open-field test (OFT) showed that both values were markedly lower in the model than in the control group; in contrast, the immobility time (IT) in the forced-swimming test (FST) was obviously higher in the model than in the control group, further confirming the successful generation of the DNP/MDD rat model (p < 0.05)
Summary
Given the high prevalence of diabetes mellitus worldwide, diabetic neuropathic pain (DNP) has become a relatively common condition [1, 2]. DNP is one of the main symptoms of diabetic neuropathy, its pathophysiological mechanisms are not yet fully understood [5]. Depression, known as major depressive disorder (MDD), is a serious medical condition affecting public health. Mild and severe depression is closely associated with increased mortality rates in patients with diabetes mellitus [6]. Painful diabetic polyneuropathy is a greater determinant of depression than other diabetes-related complications and comorbidities [7], and depression severity depends on the intensity of pain [8]. The relevant mechanisms have not been thoroughly elucidated and require further research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
