Capsaicin Summary Paper

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Capsaicin is a natural product of capsicum peppers, that is an active ingredient in many hot foods. When nociceptors- neurons that transmit information regarding tissue damage to pain-processing centers in the spinal cord and brain- come in contact with capsaicin, the neuron gets excited, and there is a perception of pain, and the a local release of inflammatory mediators. These nociceptors get excited by increasing permeability of plasma membrane to cations, but the molecular mechanism explaining this phenomenon is unclear. Capsaicin is being used in an analgesic agent in the treatment of painful disorders, causing long-term loss of responsiveness because it kills off the nociceptor, or it destroys the peripheral terminals. It was decide that the existence of a receptor site represents the most likely mechanism, because the capsaicin derivative showed structure-function relationships and evoked responses in a dose-dependent manner. A competitive capsaicin antagonist called capsazepine strengthened this model, along with discovering resiniferatoxin, an extremely potent capsaicin analogue for Euphorbia plants that mimics the cellular action of capsaicin. The cloning of a gene encoding a capsaicin receptor was decided to help develop more understanding of the molecular nature of capsaicin action and its relationship to endogenous pain signaling mechanisms. A cDNA clone that reconstitutes capsaicin responsiveness in non-neuronal cells was isolated. It was discovered that capsaicin gives off burning sensations through the activation of a heat-gated ion channel that is likely to contribute to the detection of painful thermal stimuli in vivo. Since the molecular structure of capsaicin receptors was not known, the experimenters adopted a functional screening strategy for isolating candidate cDNA clones. Because capsaicin has the ability to trigger robust calcium influx

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