Painful diabetic neuropathy(PDN)is a diabetes mellitus complication.Unfortunately,the mechanisms underlying PDN are still poorly understood.Adenosine triphosphate(ATP)-gated P2X7 receptor(P2X7R)plays a pivotal role in...Painful diabetic neuropathy(PDN)is a diabetes mellitus complication.Unfortunately,the mechanisms underlying PDN are still poorly understood.Adenosine triphosphate(ATP)-gated P2X7 receptor(P2X7R)plays a pivotal role in non-diabetic neuropathic pain,but little is known about its effects on streptozotocin(STZ)-induced peripheral neuropathy.Here,we explored whether spinal cord P2X7R was correlated with the generation of mechanical allodynia(MA)in STZ-induced type 1 diabetic neuropathy in mice.MA was assessed by measuring paw withdrawal thresholds and western blotting.Immunohistochemistry was applied to analyze the protein expression levels and localization of P2X7R.STZ-induced mice expressed increased P2X7R in the dorsal horn of the lumbar spinal cord during MA.Mice injected intrathecally with a selective antagonist of P2X7R and P2X7R knockout(KO)mice both presented attenuated progression of MA.Double-immunofluorescent labeling demonstrated that P2X7R-positive cells were mostly co-expressed with Iba1(a microglia marker).Our results suggest that P2X7R plays an important role in the development of MA and could be used as a cellular target for treating PDN.展开更多
基金Project supported by the National Natural Science Foundation of China(Nos.81771208 and 81971043)the Health and Family Planning Commission of Wuxi(No.YGZXM1406)+3 种基金the Wuxi Municipal Bureau on Science and Technology(No.CSE31N1614)the Fundamental Research Fund of Wuxi People’s Hospital(No.RKA201720)the Technology for Social Development Project of Kunshan(No.KS1539)China.
文摘Painful diabetic neuropathy(PDN)is a diabetes mellitus complication.Unfortunately,the mechanisms underlying PDN are still poorly understood.Adenosine triphosphate(ATP)-gated P2X7 receptor(P2X7R)plays a pivotal role in non-diabetic neuropathic pain,but little is known about its effects on streptozotocin(STZ)-induced peripheral neuropathy.Here,we explored whether spinal cord P2X7R was correlated with the generation of mechanical allodynia(MA)in STZ-induced type 1 diabetic neuropathy in mice.MA was assessed by measuring paw withdrawal thresholds and western blotting.Immunohistochemistry was applied to analyze the protein expression levels and localization of P2X7R.STZ-induced mice expressed increased P2X7R in the dorsal horn of the lumbar spinal cord during MA.Mice injected intrathecally with a selective antagonist of P2X7R and P2X7R knockout(KO)mice both presented attenuated progression of MA.Double-immunofluorescent labeling demonstrated that P2X7R-positive cells were mostly co-expressed with Iba1(a microglia marker).Our results suggest that P2X7R plays an important role in the development of MA and could be used as a cellular target for treating PDN.
