Role Of Spinal PTP1B In Diabetic Neuropathic Pain

Objective: Protein tyrosine phosphatase 1B(PTP1B)has been shown to dephosphorylate and inactivate insulin receptors,which contributes to diabetes.Neuropathic pain is a severe complication that results from diabetic neuropathy.The current study investigated the potential role of spinal PTP1 B in diabetic neuropathic pain.Method: The distribution pattern of PTP1 B in spinal cord dorsal horn of adult male Sprague-Dawley rats was investigated by immunohistochemistry.Western blot was used to examine the expression and function of PTP1 B in streptozotocin-injected diabetic rats.The effects of PTP1 B inhibition on diabetic neuropathic pain were measured.Results:(1)PTP1B is specifically expressed in spinal dorsal horn neurons,whereas PTP1 B is not expressed in astrocytes and microglia.(2)Diabetes induced mechanical hyperalgesia in rats.(3)Diabetes induced thermal hyperalgesia in rats.(4)Diabetic neuralgia can increase the expression of PTP1 B in spinal dorsal horn.(5)Diabetic neuralgia can enhance the localization of PTP1 B in excitatory glutamatergic synapses.(6)The designed small interfering RNA(si RNA)effectively knockdowned the expression of PTP1 B in rat spinal dorsal horn.(7)PTP1B-si RNA can effectively block hyperalgesia induced by diabetes in rats by reducing the expression of PTP1 B.(8)PTP1B-si RNA can block diabetes-induced hyperalgesia in rats.(9)The role of PTP1 B in diabetic neuralgia is closely related to the reduction of phosphorylation of Src 529 tyrosine residues(Tyr529)and Src activation.(10)PTP1B-activated Src promotes phosphorylation of tyrosine 1472 of the NMDA receptor Glu N2 B subunit.(11)PTP1B chemical inhibitors can dose-dependently increase the paw withdrawal thresholds in diabetic rats.(12)PTP1B chemical inhibitors can dose-dependently increase the paw withdrawal latency in diabetic rats.(13)Spinal dorsal horn transfection PTP1B(C215S)(215 cysteine mutation to serine)can effectively relieve diabetes-induced neuropathic pain.Conclusions: Diabetic neuropathy activated PTP1 B in spinal cord dorsal horn,inhibition of which ameliorated diabetic neuropathic pain.