Neonatal cystitis leads to alterations in spinal corticotropin releasing factor receptor-type 2 content and function in adult rats following bladder re-inflammation.

Spinal mechanisms associated with visceral hypersensitivity are poorly understood. One model of bladder hypersensitivity with phenotypic features similar to the disorder interstitial cystitis/bladder pain syndrome is the neonatal bladder inflammation (NBI) model. In this model, rat pup bladders are infused with zymosan solutions on post-partum days 14-16 and then rats are retested as adults. Studies of other sites of deep tissue hypersensitivity have suggested a role for corticotropin-releasing factor (CRF) receptors type 1 and 2 (CRFR1 and CRFR2). Using neurochemical measures, pharmacological manipulations and both reflex and neuronal responses to urinary bladder distension as endpoints, the present study probed the role of CRFR2s in bladder hyperalgesia secondary to NBI and acute bladder re-inflammation as an adult (ABI). ELISA measures of the lumbosacral spinal cord demonstrated increased CRFR1s and CRFR2s following pretreatment with both NBI + ABI as well as NBI-related increases in the CRFR2 agonist urocortin 2. Intrathecal CRFR2 antagonists, but not a CRFR1 antagonist, blocked the augmentation of visceromotor responses to distension following pretreatment with both NBI + ABI. Lumbosacral dorsal horn neuronal responses to distension in rats pretreated with NBI + ABI were attenuated by the spinal topical administration of a CRFR2 antagonist. These studies suggest therapeutic value of CRFR2 antagonists in the treatment of painful bladder disorders.
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