The role of C-fibers in the development of chronic psychological stress induced enhanced bladder sensations and nociceptive responses: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study

Neurourol Urodyn. 2018 Feb;37(2):673-680. doi: 10.1002/nau.23374. Epub 2017 Aug 9.


Aims: To evaluate C fiber-mediated changes in bladder sensation and nociception in an animal model of stress induced bladder hyperalgesia and urinary frequency.

Methods: Female Wistar-Kyoto (WKY) rats were exposed to a chronic (10 days) water avoidance stress (WAS) and compared to controls. Rats were evaluated by cystometrogram (CMG) and visceromotor reflex (VMR) to bladder infusion with room temperature (RT) or cold saline. Cold saline activates afferent C-fibers via cold bladder receptors. To further evaluate bladder hyperalgesia, CMG and VMR were also obtained during RT isometric bladder distention (RT-iBD) at variable pressures.

Results: During RT infusion, WAS rats had significant decreases in pressure threshold (PT) and in the ratio of VMR threshold/maximum intravesical pressure (IVPmax), and a significant increase in VMR duration. Cold infusion also induced significant decreases in PT and in the ratio of VMR threshold/IVPmax in WAS rats. During RT-iBD, rats exposed to WAS showed a significant decrease in VMR latency and a significant increase in VMR area under the curve (AUC) compared to controls.

Conclusion: Chronic WAS induced bladder hypersensitivity manifested by earlier voiding with earlier VMR appearance. Chronic stress also enhanced bladder nociceptive responses. WAS leads to increase responses to ice cold water infusion, implying a role of sensitized C-fibers and mechanoreceptors in WAS-induced bladder dysfunction and hypersensitivity.

Keywords: bladder hypersensitivity; cystometrogram; hyperalgesia; interstitial cystitis; visceromeotor reflex; water avoidance stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Nerve Fibers, Unmyelinated / physiology*
  • Nociception / physiology*
  • Pelvic Pain / etiology
  • Pelvic Pain / physiopathology*
  • Rats
  • Rats, Inbred WKY
  • Stress, Psychological / complications
  • Stress, Psychological / physiopathology*
  • Urinary Bladder / physiopathology*