Inhibition of YAP/TAZ Activity in Spinal Cord Suppresses Neuropathic Pain.

UNLABELLED: Neuropathic pain, often caused by nerve injury, is a major clinical challenge. Mechanisms that underlie neuropathic pain remain elusive and effective medications are limited. Numerous investigations of pain mechanisms have focused on alterations and phenotypic switches of the nociceptive transmitters and modulators, as well as on their receptors and downstream signaling pathways that have already exerted roles in the pain processes of mature nervous systems. We have demonstrated recently that nerve injury may elicit neuronal alterations that recapitulate events occurring during development. Signaling of the representative activated molecule Wnt thus becomes a trigger for the development of neuropathic pain and is a potential therapeutic target. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the ß-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status in rats. Peripheral nerve injury causes rapid-onset and long-lasting nuclear accumulation of YAP/TAZ/ß-catenin in the spinal dorsal horn. Spinal inhibition or knock-down of either YAP or TAZ suppresses mechanical allodynia induced by nerve injury or the pain initiators lysophosphatidic acid and Wnt3a. Promoting the nuclear accumulation of YAP/TAZ leads to mechanical hypersensitivity in naive animals. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/ß-catenin and can greatly suppress neuropathic pain and the associated neurochemical alterations. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening for potent analgesics for the treatment of neuropathic pain. SIGNIFICANCE STATEMENT: Mechanisms that underlie neuropathic pain remain elusive. We have demonstrated recently that nerve injury can activate Wnt signaling, which becomes a trigger for the development of neuropathic pain. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the ß-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/ß-catenin and can greatly suppress neuropathic pain. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening of potent analgesics for the treatment of neuropathic pain.

Effects observation of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis / 中国生化药物杂志

Objective To investigate the clinical effects of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis. Methods 100 patients with chronic cholestatic hepatitis were selected from Pingyang Hospital of traditional Chinese medicine from February 2011 to November 2016. They were randomly divided into the study group (n=50) and the control group (n=50). The control group was given routine treatment, the study group on the basis of routine therapy was given modified Yinchenzhufu decoction. The clinical efficacy and adverse reactions (drug related) during the 8 weeks of continuous treatment were recorded in two groups of patients with chronic cholestatic hepatitis. Results After treatment, the total efficiency in the study group of patients with chronic cholestatic hepatitis was 90.00% and the control group was 72.00%, and there was significant difference between two group (P<0.05); there was no statistical significance in adverse reactions of treatment in the study group, compared with the control group. Conclusion The application of the basic method of treatment for chronic cholestatic hepatitis plus modified Yinchenzhufu decoction could significantly improve the clinical efficacy.

Effects observation of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis / 中国生化药物杂志

Objective To investigate the clinical effects of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis. Methods 100 patients with chronic cholestatic hepatitis were selected from Pingyang Hospital of traditional Chinese medicine from February 2011 to November 2016. They were randomly divided into the study group (n=50) and the control group (n=50). The control group was given routine treatment, the study group on the basis of routine therapy was given modified Yinchenzhufu decoction. The clinical efficacy and adverse reactions (drug related) during the 8 weeks of continuous treatment were recorded in two groups of patients with chronic cholestatic hepatitis. Results After treatment, the total efficiency in the study group of patients with chronic cholestatic hepatitis was 90.00% and the control group was 72.00%, and there was significant difference between two group (P<0.05); there was no statistical significance in adverse reactions of treatment in the study group, compared with the control group. Conclusion The application of the basic method of treatment for chronic cholestatic hepatitis plus modified Yinchenzhufu decoction could significantly improve the clinical efficacy.