| Summary: | 碩士 === 國防醫學院 === 生物化學研究所 === 104 === Abstract
Neuropathic pain is the most debilitating of all clinical pain syndromes, may be a consequence of pathology from diseases that affect the central or peripheral nervous system. In patients, neuropathic pain is mainly related to with diabetes, post-herpetic neuralgia or cancer and is nearly always resistant to general analgesics, such as non-steroidal anti-inflammatory drugs or even opioids. The extracellular mediator ATP, by activating ionotropic P2X and metabotropic P2Y receptors, participates significantly in the generation and modulation of various forms of pain. P2XRs are responsible for cancer neuropathic pain. Hericium erinaceus is famous as a potent stimulator to facilitate the gene expression of nerve growth factor and is supposed to have potential for neurodegenerative disease treatments. In this study, mushroom extracts on mice pain behavior after nerve ligation (L5 spinal nerve ligation) and cellular damage induced by cancer-chemotherapy drugs are examined.
Several cell lines were used in this study, including human osteosarcoma HOS cells, rat-mice hybrid NG-108-15 cells. The subtypes of P2X and P2Y in each cells and their gene expression during different treatments were investigated by RT-PCR. The calcium signaling coupled with P2R were measured via calcium fluorescent dye, fura-2. Cytoviability was measured by MTT.
This study show that several subtypes of P2X and P2Y exist in HOS cells and NG108-15 cells but ATP-induced an elevation of cytosolic calcium concentration ([Ca2+]c) only exists in HOS cells. The mushroom extracts reduce mice pain responses induced by nerve ligation and reduced the ATP induced a rise in [Ca2+]c. the analgesic effects of natural complex might be from their suppression of P2R. Oxaliplatin (OXA) and paclitaxel (PTX) both have cytotoxicity in NG108-15 cells that can be suppressed by the mushroom extracts. OXA or PTX induce the production of ROS and NO that can be suppressed by the mushroom extracts. Conclusively, the mushroom extracts can reduce the cytotoxicity, ROS production and NO synthesis caused by cancer therapy drugs that illustrates the mushroom extracts might have cellular protection roles. The mushroom extracts can suppress P2R coupled calcium signaling and nerve ligation-induced mice pain behavior. Further studies are worth and necessary to evidence the potential of the mushroom extracts using for neuronal protection and pain release.
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