5-HT2B regulated calcium response mediating mechanical hyperalgesia

• Main Authors: Shih-yuan Lin, 林詩媛
• Other Authors: Wei-hsin Sun
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/07159671558651168966

碩士 === 國立中央大學 === 生命科學研究所 === 100 === Serotonin (5-Hydroxytryptamine, 5-HT) is one of the important inflammatory mediators in pain and hyperalgesia. 5-HT released from mast cells or platelets in peripheral tissues, can directly act on 5-HT-gated ion channel (5-HT3) to change sodium and calcium permeability and excitability of nociceptors. 5-HT can also induce chemical interaction through the activation of 5-HT G-protein coupled receptors (5-HT1, 2, 4, 5, 6, 7). Previous studies have found that 5-HT2B is highly localized in small-to-medium diameter (10-34 μm) dorsal root ganglion (DRG) neurons but not 5-HT2C. The antagonist of 5-HT2B/2C inhibits 5-HT-induced mechanical hyperalgesia. However, it remains unclear whether 5-HT2B-mediated 5-HT signaling is involved in 5-HT-induced mechanical hyperalgesia and detailed mechanisms. To address this question, I have injected 5-HT and 5-HT2B/2C antagonist into mouse hind paw and DRG were taken from injected mice to culture. Cultured neurons were stimulated by 5-HT, followed by calcium imaging. Three patterns of 5-HT-induced intracellular calcium increase were found: transient, sustained and mixed. After 5-HT-injection, the number of 5-HT-responding neurons had 2.6-fold increase (5.1% vs. 13.3%) and the 5-HT-induced calcium increase was 2.4-fold increased on ipsilateral IB4-negative neurons but not on IB4-positive neurons. 5-HT2B/2C antagonist injection reduced the number of 5-HT-responding neurons (1.3%) and inhibited the transient [Ca2+]i rise in patterns 1 and 2. I also found that capsaicin-induced calcium influx was increased on IB4-negative neurons after 5-HT-injection and the increased calcium influx was inhibited by 5-HT2B/2C antagonist. Interestingly, 5-HT-induced sodium current was not enhanced by 5-HT injection but reduced by injection of 5-HT2B/2C antagonist. These results suggest that 5-HT2B-mediated calcium response is involved in 5-HT-induced mechanical hyperalgesia.