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P2X7 receptor is a crucial receptor related to neuronal activation, neurosensitization, and pain transmission, and increasing evidences indicated that glial cells is thought to be a major contributor to the chronic neuropathic pain after nerve injury. In present study, we designed to investigate whether the P2X7R in glial plays a role in chronic neuropathic pain. We divided adult male Sprague Dawley rats were respectively into four groups:(1) vehicle group (Veh), (2) CCI (C group), (3) P2X7 inhibitor group (P group), (4) CCI+ P2X7R inhibition (CP group). Behavior test, real-time polymerase chain reaction, western blot, immunofluorescence staining, and transmission electron microscope were used to analyze the scientific hypothesis. The results of the experiment is that(i) P2X7R of microglia was downregulated by A-70003 after CCI. (ii) Downregulation of P2X7R on microglia is coincident with remission of NP after CCI. (iii) P2X7R of microglia participates in NP via regulating autophagy and apoptosis. In summary, our results support P2X7R inhibition can counteract the CCI-induced NP due to microglia activation via a modulation of autophagy and apoptosis in mPFC and spinal cord. This may provide an importantly neuroprotective mechanism for the improved NP and also help devising new therapeutic to improve chronic pain in patients.

DMH1 (D4-[6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline) is a bone morphogenetic protein antagonist. However, the influence of DMH1 on colorectal cancer metastasis remains unknown. Hence, This study aimed to investigate the inhibitory effect of DMH1 on the migration of cancer cells. In vitro incubation with DMH1(1mM) inhibited the high protein level of HIF-1α in CT-26 cells. Transwell assay confirmed that DMH1 suppress CT-26 cells migration via the HIF-1α under hypoxia. The accumulation of lactate in culture medium down-regulated the extracellular pH, then stimulated the migration of CT-26 cells. DMH1 suppressed the migration of CT-26 cells through HIF-1α/MCT-4 signaling pathway mediate the excreation of lactate. The data demonstrated that DMH1 downregulated the high intracellular pH levels via the HIF-1α/MCT-4 signaling pathway to mediate lactate excretion. This study indicated that DMH1 might serve as a potential drug for treating tumor migration by minimizing the intracellular pH via the HIF-1α/MCT-4 signaling pathway.