| Summary: | 博士 === 國立陽明大學 === 跨領域神經科學國際研究生博士學位學程 === 107 === Itch or pruritus is an unpleasant sensory sensation that causes discomfort and a desire to scratch. Pruriception occurs when pruritogens (e.g. histamine, chloroquine, etc.) evoke chemical itch by activating the pruritogen-specific primary sensory neuron. Through spinothalamic tract in the spinal cord, the itch sensation relays to higher brain centres, bringing a desire to scratch. Scratching is often accompanied by the application of counter stimuli, such as pain, to inhibit itch by activating the inhibitory interneurons in the spinal cord dorsal horn. However, how this scratching (or noxious mechanical stimuli) relieves itch is still a mysterious puzzle. In the process of solving this puzzle, I found that the no-nail-scratching (rubbing) also relieved itch in mice, and the itching mice preferred to rub an itch over scratch upon prolonged daily treatment of pruritogen-evoked chemical itch. Also I observed, through the conditioned place preference test, these scratching and rubbing counterstimuli, brought rewarding effect in mice ,while relieving itch. Supporting this behavioural observation. The Micro-PET studies confirmed the role of dopamine in the limbic system for the rewarding effect observed while relieving itch through scratching and rubbing counter-stimuli. Therefore, I aimed to address the neurobiological basis of itch relief through the no-nail scratching (rubbing). Through immunohistochemical studies, I found that the sensory neurons responding to rubbing stimuli were IB4-positive (non peptidergic) C-fiber neurons. Then, I found a more specific subset of IB4- positive neurons expressing MrgprB4 were possible candidates for rubbing-induced itch relief. Through genetic ablation and chemical optogenetic studies, I have found that MrgprB4 positive neurons are involved in itch relief through rubbing. With retrograde tracing studies, I found that MrgprB4 positive neurons forming synapses with B5-I neurons at the second layer of the spinal cord dorsal horn, in which the B5-I neurons inhibit the pruriceptive afferent inputs to relieve the itch. Through in-situ hybridization studies, I found that piezo 2 ion channel is expressed in MrgprB4 positive neurons, which could be the possible mechanosensitive ion channel responding to the nonnoxious mechanical stimuli - rubbing. To the other end , I found ASIC-1b positive neurons were possible candidates for scratching-induced itch relief and ASIC-1b ion channels were absent in MrgprB4 positive neurons, suggesting scratching and rubbing induced itch relief through different peripheral pathways.
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