研究期間：10108~10207;Non-steroid anti-inflammatory drugs are well-known drugs against inflammatory pain, but also have side effects. Understanding of the molecular mechanism of inflammatory pain is important to identify specific targets for clinical treatment. Inflammation resulting from tissue injury, infection or tumor growth often produces chemical mediators (such as 5-HT, prostaglandin E2, bradykinin), inducing chronic and persistent pain. Serotonin released from mast cells or platelets in the peripheral tissues is one of important inflammatory mediators in causing pain and hyperalgesia. The presence of multiple 5-HT receptors on primary afferent nociceptors reflects 5-HT-induced pain or hyperalgesia through different receptors with distinct mechanisms. Despite the potential importance of 5-HT in hyperalgesia, the involvement of 5-HT receptor subtypes in hyperalgesia and cellular mechanisms remain to be clarified. Our preliminary experiments have found that antagonist of 5-HT2B/2C inhibits 5-HT-induced mechanical hyperalgesia. Given that 5-HT2C is not present in DRG neurons and antagonist inhibition is a short-time effect, suggesting that 5-HT2B is involved in 5-HT-induced mechanical hyperalgesia. However, whether 5-HT2B participates 5-HT-induced pain and what is molecular mechanism of 5-HT2B-mediated hyperalgesia remain unclear. The objective of this application is to elucidate the role of serotonin receptor, 5-HT2B in pain. The central hypothesis of this application is that 5-HT2B mediates 5-HT signaling to regulate ion channels related to mechanical hyperalgesia. The proposed work is innovative, as it is the first study to determine the role of 5-HT2B in pain. It is expected to yield the following outcomes: elucidation of molecular mechanism of 5-HT2B–mediated mechanical hyperalgesia and elucidation of involvement of 5-HT2B in inflammatory pain. These results will be important because they are expected to facilitate understanding of molecular mechanisms of inflammatory pain and to fundamentally advance the fields of pain research and development of new anti-inflammatory drugs.
