Spinal microglial M1 polarization contributes paclitaxel-induced neuropathic pain by triggering cells necroptosis.

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.

Multi-central clinical evaluation of ginger-partitioned moxibustion for treatment of leukopenia induced by chemotherapy / 中国针灸

<p><b>OBJECTIVE</b>To prove the therapeutic effect of ginger-partitioned moxibustion on leukopenia induced by chemotherapy and effect on life quality of the patient with tumor after chemotherapy.</p><p><b>METHODS</b>Randomized, controlled, multi-central cooperative method was used and the patients confirmed to the enrolled criteria were divided in-to two groups. The test group were treated with ginger-partitioned moxibustion at Dazhui (GV 14), Geshu (BL 17), Pishu (BL 20), etc.; and the control group with oral administration of Chinese patent medicine.</p><p><b>RESULTS</b>Out of the 221 cases confirmed to program analysis, 113 cases were in the test group and 108 cases in the control group. After 10 days, the cured rate and the effective rate were 84.1% and 66.4% in the test group and 35.2% and 33.3% in the control group, respectively, with very significant differences between the two groups (both P < 0.01); fifteen days later, the therapeutic effects in the two groups were maintained. The two methods could improve clinical symptoms, with the test group being better than the control group. Any adverse response was not found in the two groups, and the injuries of functions of the heart, lung and kidney induced by chemotherapy had some improvement.</p><p><b>CONCLUSION</b>The therapeutic effect of ginger-partitioned moxibustion on luekopenia induced by chemotherapy is reliable and is better than oral administration of Chinese patent medicine, with a better duplication.</p>