A central mechanism of analgesia in mice and humans lacking the sodium channel NaV1.7.
作者： Robert M. Brownstone , Frank Zufall , Queensta Millet , Shafaq Sikandar , James J. Cox
DOI: 10.1016/J.NEURON.2021.03.012
关键词: Anosmia 、 Neurotransmitter 、 Biology 、 Endogenous opioid 、 Calcium imaging 、 Neurotransmission 、 Opioid 、 Nociceptor 、 Knockout mouse 、 Neuroscience
摘要: Summary Deletion of SCN9A encoding the voltage-gated sodium channel NaV1.7 in humans leads to profound pain insensitivity and anosmia. Conditional deletion sensory neurons mice also abolishes pain, suggesting that locus analgesia is nociceptor. Here we demonstrate, using in vivo calcium imaging extracellular recording, knockout have essentially normal nociceptor activity. However, synaptic transmission from central terminals spinal cord greatly reduced by an opioid-dependent mechanism. Analgesia reversed substantially but not peripheral application opioid antagonists. In contrast, lack neurotransmitter release olfactory independent. Male female with NaV1.7-null mutations show naloxone-reversible analgesia. Thus, inhibition principal mechanism anosmia mouse human Nav1.7-null mutants.
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