Footshock-Induced Urinary Bladder Hypersensitivity: Role of Spinal Corticotropin-Releasing Factor Receptors

Academic Article

Abstract

  • Stress-induced hyperalgesia (SIH), a common clinical observation associated with multiple painful diseases including functional urinary disorders, presently has no mechanistic explanation. Using a footshock treatment, a classic stressor, to magnify physiological responses in a model of urinary bladder pain, we examined one potential group of mediators of SIH, the corticotropin-releasing factor (CRF)-related neuropeptides. Exposure to a footshock treatment produced bladder hypersensitivity in female Sprague-Dawley rats, manifested as significantly more vigorous visceromotor responses (VMRs) to urinary bladder distension (UBD) compared with rats that were exposed to a non-footshock treatment. This bladder hypersensitivity was significantly attenuated by blocking spinal CRF2 receptors but not CRF1 receptors. Furthermore, spinal administration of urocortin 2, a CRF2 receptor agonist, augmented UBD-evoked VMRs in a way similar to what was observed after exposure to Footshock, an effect significantly attenuated by pretreatment with spinal aSVG30, a CRF2 receptor antagonist. Surprisingly, neither spinal administration of CRF nor the CRF1 receptor antagonist antalarmin had an effect on bladder nociceptive responses. The results of the present study not only provide further support for a role of stress in the exacerbation of bladder pain but also implicate spinal urocortins and their endogenous receptor, the CRF2 receptor, as potential mediators of this effect. Perspective: This study presents evidence that spinal urocortins and CRF2 receptors are involved in stress-induced hypersensitivity related to the urinary bladder. This provides a basis for investigating how urocortins mediate SIH, ultimately leading to more effective treatment options for patients with painful bladder syndromes as well as stress-exacerbated chronic pain. © 2008 American Pain Society.
  • Published In

  • Journal of Pain  Journal
  • Digital Object Identifier (doi)

    Author List

  • Robbins MT; Ness TJ
  • Start Page

  • 991
  • End Page

  • 998
  • Volume

  • 9
  • Issue

  • 11