Footshock-induced urinary bladder hypersensitivity: role of spinal corticotropin-releasing factor receptors.
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 CRF(2) receptors but not CRF(1) receptors. Furthermore, spinal administration of urocortin 2, a CRF(2) 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 CRF(2) receptor antagonist. Surprisingly, neither spinal administration of CRF nor the CRF(1) 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 CRF(2) receptor, as potential mediators of this effect.


CONCLUSIONS
This study presents evidence that spinal urocortins and CRF(2) 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.
Robbins
Meredith T
MT
Department of Anesthesiology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294, USA. mturnbach@yahoo.com
Ness
Timothy J
TJ
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D004576:Electromyography / Q000379:methods; D004597:Electroshock / Q000009:adverse effects / Q000379:methods*; D005260:Female; D005528:Foot; D007278:Injections, Spinal; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000503:physiopathology*; D054832:Urocortins / Q000008:administration & dosage / Q000494:pharmacology; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
D010446:Peptide Fragments; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C103016:antalarmin; C116607:antisauvagine 30; D003346:Corticotropin-Releasing Hormone