Streptozotocin-induced diabetic hyperalgesia in rats is associated with upregulation of Toll-like receptor 4 expression.
Neuropathic pain is one of the common complications of diabetes mellitus, and current treatments often do not meet medical needs. Toll-like receptor 4 (TLR4) has been implicated as a potential therapeutic target in neuropathic and other pain models. In this study, we investigated whether TLR4 expression in spinal cord would be altered in streptozotocin-induced diabetic rat model, which had persistent mechanical and thermal hypersensitivity. The results showed that the mRNA expression of TLR4 was upregulated in streptozotocin-treated animals. Furthermore, TLR4 expression was associated with both paw-pressure withdrawal threshold toward mechanical stimulus and paw withdrawal latency toward thermal stimulus. The protein levels of TNF-α and IL-1β, two downstream proinflammatory cytokines of TLR4 signaling pathway, were also significantly raised and correlated with mechanical/thermal hypersensitivity in diabetic rats. Together, these data have demonstrated that TLR4 and its signaling pathway are associated with neuropathic pain in a diabetic model. It may imply that TLR4 could be a novel target for treating diabetic neuropathy.
Department of Anesthesia, Guiyang Medical College, Guiyang, China.
Jian-E
JE
Yan
Wei
W
Yuan
Xiaoli
X
Lou
Tao
T
Zhu
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism; D013311:Streptozocin; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014110:Touch; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D053583:Interleukin-1beta; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin