ASIC3 gene deletion modulates M1/M2 macrophage ratio to attenuate thermal hyperalgesia induced by chronic constriction injury of the sciatic nerve

• Main Authors: Yi-Chu Huang, 黃翊筑
• Other Authors: Wei-Hsin Sun
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/6x7ck7

碩士 === 國立中央大學 === 生命科學系 === 107 === Neuropathic pain is a pain initiated or caused by a primary lesion or dysfunction in the nervous system. Symptoms include spontaneous pain, dysaesthesia, paraesthesia, allodynia and hyperalgesia. Neuropathic pain often accompanies with neuroinflammation, immune responses, satellite glial cells (SGCs) activation and neuron loss. Local tissue acidosis is a major factor to regulate inflammation and induce pain. Acid-sensing ion channel 3 (ASIC3), one of proton-sensing receptors, directly or indirectly mediates pain and hyperalgesia. However, it remains unclear whether is involved in neuropathic pain. I have established a model chronic constriction injury of sciatic nerves (CCI) to explore the role of ASIC3 in neuropathic pain. I have found that CCI mice developed long-term mechanical hyperalgesia and thermal hyperalgesia. In ASIC3-/- mice, the long-term thermal hyperalgesia induced by CCI was reduced from the first week and the inhibitory effect was maintained for 14W. Histochemistry analysis of injured nerve demonstrated that CCI mice developed long-term inflammation with granulocytes and macrophages. In ASIC3-/- mice, the number of macrophages were significantly increased compared to ASIC3+/+ at the first week but decreased at 4, 8W. I have found that ASIC3 deletion decreased the number of pro-inflamatory macrophage (M1), but increased the number of anti-inflamatory macrophage (M2) after CCI surgery. Accordingly, ASIC3 may involve in thermal hyperalgesia induced by peripheral nerve injury via modulates the proportion of M1 / M2 macrophages ratio.