Nerve sprouting and neurogenic inflammation characterize the neurogenic detrusor overactive bladder of patients no longer responsive to drug therapies

J Cell Mol Med. 2019 Jun;23(6):4076-4087. doi: 10.1111/jcmm.14294. Epub 2019 Apr 3.

Abstract

Urothelium and Lamina Propria (LP) are considered an integrate sensory system which is able to control the detrusor activity. Complete supra-sacral spinal cord lesions cause Neurogenic Detrusor Overactivity (NDO) whose main symptoms are urgency and incontinence. NDO therapy at first consists in anti-muscarinic drugs; secondly, in intra-vesical injection of botulinum toxin. However, with time, all the patients become insensitive to the drugs and decide for cystoplastic surgery. With the aim to get deeper in both NDO and drug's efficacy lack pathogenesis, we investigated the innervation, muscular and connective changes in NDO bladders after surgery by using morphological and quantitative methodologies. Bladder innervation showed a significant global loss associated with an increase in the nerve endings located in the upper LP where a neurogenic inflammation was also present. Smooth muscle cells (SMC) anomalies and fibrosis were found in the detrusor. The increased innervation in the ULP is suggestive for a sprouting and could condition NDO evolution and drug efficacy length. Denervation might cause the SMC anomalies responsible for the detrusor altered contractile activity and intra-cellular traffic and favour the appearance of fibrosis. Inflammation might accelerate these damages. From the clinical point of view, an early anti-inflammatory treatment could positively influence the disease fate.

Keywords: anti-muscarinic drugs; botulinum toxin; detrusor; immunohistochemistry; lamina propria; nerve sprouting; neurogenic detrusor overactivity; neurogenic inflammation; transmission electron microscopy; urinary bladder innervation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Botulinum Toxins, Type A / therapeutic use
  • Female
  • Humans
  • Male
  • Mucous Membrane / drug effects
  • Mucous Membrane / pathology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / pathology
  • Neurogenic Inflammation / drug therapy
  • Neurogenic Inflammation / pathology*
  • Urinary Bladder / drug effects
  • Urinary Bladder / pathology*
  • Urinary Bladder, Overactive / drug therapy
  • Urinary Bladder, Overactive / pathology*
  • Urinary Incontinence / drug therapy
  • Urinary Incontinence / pathology
  • Urothelium / pathology

Substances

  • Botulinum Toxins, Type A