title: Sensory innervation of the external genital tract of female guinea pigs and mice.
abstract: BACKGROUND
  The structural and neurochemical characterization of the sensory innervation of the external genitalia of females is poorly known.
  
  
  OBJECTIVE
  To immunohistochemically map the sensory innervation of external genitalia and surrounding structures of female guinea pigs and mice.
  
  
  METHODS
  Large-diameter sensory fibers, presumably mechanoreceptors, were identified by their immunoreactivity to neuron-specific enolase (NSE) or vesicular glutamate transporter 1 (VGluT1). Peptidergic sensory fibers, presumably unmyelinated nociceptors, were identified by their immunoreactivity to calcitonin gene-related peptide (CGRP), substance P, or both. Multiple-labelled tissues were examined with high-resolution confocal microscopy.
  
  
  METHODS
  Microscopic identification of sensory endings, including potential nociceptors, characteristic of the external genitalia.
  
  
  RESULTS
  Large complex nerve endings immunoreactive for NSE and VGluT1 were abundant in dermal papillae of the clitoris. Each large ending was accompanied by one or two fine fibers immunoreactive for CGRP but neither substance P nor VGluT1. More simple NSE-immunoreactive endings occurred within dermal papillae in non-hairy skin of the labia and anal canal but were rare in pudendal or perineal hairy skin. Fine intra-epithelial fibers immunoreactive for NSE but not CGRP were abundant in hairy skin but rare in non-hairy genital skin and the clitoris. Only fine varicose fibers immunoreactive for both CGRP and substance P occurred in connective tissue underlying the mucosal epithelium of cervix and endometrium.
  
  
  CONCLUSIONS
  Compared with surrounding tissues, the sensory innervation of the clitoris is highly specialized. The coactivation of nociceptors containing CGRP but not substance P within each mechanoreceptor complex could be the explanation of pain disorders of the external genitalia.
authors.affiliation: Anatomy and Histology and Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia.
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Vilimas
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Yuan
authors.forename: Rainer V
authors.initials: RV
authors.lastname: Haberberger
authors.forename: Ian L
authors.initials: IL
authors.lastname: Gibbins
mesh_terms: D001003:Anal Canal / Q000294:innervation; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002987:Clitoris / Q000378:metabolism; D020405:Dermis / Q000294:innervation; D005260:Female; D005836:Genitalia, Female / Q000294:innervation*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D009619:Nociceptors / Q000378:metabolism; D010502:Perineum / Q000294:innervation; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D050598:Vesicular Glutamate Transport Protein 1; D013373:Substance P; D010751:Phosphopyruvate Hydratase; D015740:Calcitonin Gene-Related Peptide