| Neuropathic pain after peripheral nerve injury is tough, insufferable and lacking effective therapy. Previous studies have showed the roles of microglia and ATP in animal models but the underlying mechanisms are still unclear. Here we made a rat model with neuropathic pain induced with spared nerve injury (SNI), and used behaviorology, immunofluorescent staining, western blot and immuno-electronmicroscopic techniques to investigated the localization and time sequence of glial activation and P2X receptor upregulation induced with SNI. P2X receports agonists and antagonist were used as pretreataent then observed the ethology changes. We try to provide theory evidence for the prevention and cure of neuropathic pain.We found microglia activation preceded astrocyte activation after SNI. By using P2X receptors agonists produced a marked and sustained allodynia in naive rats which were well mimic the allodynia in SNI rats and the homologous antagonists for P2X4R and P2X7R suppressed the SNI induced allodynia partly or completely. In microglia, P2X4R showed a striking upregulation and peaked at 20 days after SNI then decreased steeply but P2X7R expression peaked at day 10 and decreased mildly. In astrocyte, P2X4R maintained at the basal level but P2X7R increased rapidly to a plateau at day 10 and sustained at this high level till the end. Ultrastructure localization showed the significant differences between P2X4R and P2X7R, (1) P2X4R expressed in the postsynaptic element while P2X7R expressed in presynaptic element, (2) P2X4R expressed on the outer surface of mitochondria while P2X7R expressed on the inner surface or cristae of mitochondria, revealed the structure basis of P2XRs in pain signaling transmission and modulation.Taken together, we therefore concluded that hyperactive microglia and astrocyte were both involved in the allodynia and the time-associated upregulation of P2X4 and P2X7 receptors in glia were the potent modulators in the development of neuropathic pain.
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