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Recently, specialized<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h\u2010expressing cells embedded in the urethral epithelium have been proposed as chemosensory sentinels for detection of bacterial infection. Here, we examined the morphology and potential role in sensory signalling of a different class of specialized cells that express serotonin (5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>), termed paraneurones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Urethrae, dorsal root ganglia neurones and spinal cords were isolated from adult female mice and used for immunohistochemistry and calcium imaging. Visceromotor reflexes (<jats:styled-content style=\"fixed-case\">VMR<\/jats:styled-content>s) were recorded<jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified two morphologically distinct groups of 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sup>+<\/jats:sup>cells with distinct regional locations: bipolar\u2010like cells predominant in the mid\u2010urethra and multipolar\u2010like cells predominant in the proximal and distal urethra. Sensory nerve fibres positive for calcitonin gene\u2010related peptide, substance P, and<jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>1 were found in close proximity to 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sup>+<\/jats:sup>paraneurones.<jats:italic>In vitro<\/jats:italic>5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>(1<jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>) stimulation of urethral primary afferent neurones, mimicking 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>release from paraneurones, elicited changes in the intracellular calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) mediated by 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>2<\/jats:sub>and 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>3<\/jats:sub>receptors. Approximately 50% of 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>responding cells also responded to capsaicin with changes in the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>.<jats:italic>In vivo<\/jats:italic>intra\u2010urethral 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>application increased<jats:styled-content style=\"fixed-case\">VMR<\/jats:styled-content>s induced by urethral distention and activated<jats:styled-content style=\"fixed-case\">pERK<\/jats:styled-content>in lumbosacral spinal cord neurones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These morphological and functional findings provide insights into a putative paraneurone\u2010neural network within the urethra that utilizes 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content>signalling, presumably from paraneurones, to modulate primary sensory pathways carrying nociceptive and non\u2010nociceptive (mechano\u2010sensitive) information to the central nervous system.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12919","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T14:21:19Z","timestamp":1500387679000},"source":"Crossref","is-referenced-by-count":35,"title":["Serotonergic paraneurones in the female mouse urethral epithelium and their potential role in peripheral sensory information processing"],"prefix":"10.1111","volume":"222","author":[{"given":"F. 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