title: Genitourinary and gastrointestinal co-morbidities in children: The role of neural circuits in regulation of visceral function.
abstract: OBJECTIVE
  Pediatric lower urinary tract dysfunction (LUTD) is a common problem in childhood. Lower urinary tract symptoms in children include overactive bladder, voiding postponement, stress incontinence, giggle incontinence, and dysfunctional voiding. Gastrointestinal co-morbidities, including constipation or fecal incontinence, are commonly associated with lower urinary tract (LUT) symptoms in children, often reaching 22-34%. This review summarized the potential mechanisms underlying functional lower urinary and gastrointestinal co-morbidities in children. It also covered the current understanding of clinical pathophysiology in the pediatric population, anatomy and embryological development of the pelvic organs, role of developing neural circuits in regulation of functional co-morbidities, and relevant translational animal models.
  
  
  METHODS
  This was a non-systematic review of the published literature, which summarized the available clinical and translational studies on functional urologic and gastrointestinal co-morbidities in children, as well as neural mechanisms underlying pelvic organ 'cross-talk' and 'cross-sensitization'.
  
  
  RESULTS
  Co-morbidity of pediatric lower urinary and gastrointestinal dysfunctions could be explained by multiple factors, including a shared developmental origin, close anatomical proximity, and pelvic organ 'cross-talk'. Daily physiological activity and viscero-visceral reflexes between the lower gastrointestinal and urinary tracts are controlled by both autonomic and central nervous systems, suggesting the dominant modulatory role of the neural pathways. Recent studies have provided evidence that altered sensation in the bladder and dysfunctional voiding can be triggered by pathological changes in neighboring pelvic organs due to a phenomenon known as pelvic organ 'cross-sensitization'. Cross-sensitization between pelvic organs is thought to be mainly coordinated by convergent neurons that receive dual afferent inputs from discrete pelvic organs. Investigation of functional changes in nerve fibers and neurons sets certain limits in conducting appropriate research in humans, making the use of animal models necessary to uncover the underlying mechanisms and for the development of novel therapeutic approaches for long-term symptomatic treatment of LUTD in the pediatric population.
  
  
  CONCLUSIONS
  Pediatric LUTD is often complicated by gastrointestinal co-morbidities; however, the mechanisms linking bladder and bowel dysfunctions are not well understood. Clinical studies have suggested that therapeutic modulation of one system may improve the other system's function. To better manage children with LUTD, the interplay between the two systems, and how co-morbid GI and voiding dysfunctions can be more specifically targeted in pediatric clinics need to be understood.
authors.affiliation: Division of Urology, Department of Surgery, University of Colorado School of Medicine, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Malykhina
authors.affiliation: Division of Urology, Department of Surgery, University of Colorado School of Medicine, USA; Department of Pediatric Urology, Children's Hospital of Colorado, 13123 E 16th Avenue, Aurora, CO 80045, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Brodie
authors.affiliation: Division of Urology, Department of Surgery, University of Colorado School of Medicine, USA. Electronic address: Duncan.Wilcox@childrenscolorado.org.
authors.forename: D T
authors.initials: DT
authors.lastname: Wilcox
mesh_terms: D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D005767:Gastrointestinal Diseases / Q000175:diagnosis* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D059411:Lower Urinary Tract Symptoms / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D014551:Urinary Tract / Q000196:embryology*; D014566:Urogenital System / Q000196:embryology*
keywords: Micturition reflex; Neural pathways; Pediatric bladder and bowel dysfunction; Pelvic organ cross-sensitization; Pelvic organ cross-talk; Urologic and gastrointestinal co-morbidity