Neuronal GRK2 regulates microglial activation and contributes to electroacupuncture analgesia on inflammatory pain in mice

BACKGROUND: G protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia. METHODS: The mice model of inflammatory pain was built by subcutaneous injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and down-regulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron-specific promoters, and microglial activation and neuroinflammation were evaluated by real-time PCR. RESULTS: Intraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA-induced mechanical allodynia. The effects of EA were markedly weakened by non-cell-specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron-specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA-induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA-induced inflammatory pain. CONCLUSION: The restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.

The expression of DJ-1 gene in human hepatocellular carcinoma and its relationship with tumor invasion and metastasis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the expression of DJ-1 in human hepatocellular carcinoma and its relationship with tumor invasion and metastasis.</p><p><b>METHODS</b>Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical methods were used to detect the expression of DJ-1 mRNA and protein in tumor tissue and para-tumor tissue of 46 cases of hepatocellular carcinoma. The relationship between the expression of DJ-1 and clinicopathologic parameters was analyzed.</p><p><b>RESULTS</b>DJ-1 mRNA and protein were expressed in 69.6% and 58.7% of the tumor tissues, which were significantly higher than those in para-tumor tissues (39.1% and 34.8%), chi2 = 8.587, P < 0.05. The increased expression of DJ-1 protein was not correlated with sex of patients, size of tumor, AFP, HBsAg, differentiation level of tumor and hepatocirrhosis (P > 0.05), but with the capsula of tumor, thrombus in the portal vein (P < 0.05).</p><p><b>CONCLUSIONS</b>DJ-1 gene expression may play an important role in the invasion and metastasis of HCC.</p>