All ETDs from UAB

Advisory Committee Chair

Alan Randich

Advisory Committee Members

David C Knight

Timothy J Ness

Meredith T Robbins

Diane C Tucker

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences


In adult female rats, zymosan-induced inflammation of the bladder leads to bladder hypersensitivity, as reflected in augmented visceromotor reflex (VMR) responses to urinary bladder distension (UBD). Prior early-in-life (EIL) experience with bladder inflammation further increases bladder hypersensitivity. Naloxone increases bladder hypersensitivity in animals inflamed only as adults, but not in animals inflamed EIL, indicating that bladder inflammation recruits an inhibitory opioid system which may be impaired by EIL inflammation. This thesis examined what role the dynorphin/κ-opioid system played in mediating bladder hypersensitivity through the impairment of opioid inhibition. In all experiments, animals were treated EIL (P14-P16) and as adults with anesthesia only or zymosan. In Experiment 1, responses to a κ-opioid agonist were examined by measuring the VMR to UBD after i.v. administration of 1 mg/kg and 4 mg/kg of U50,488H. In most animals 1 mg/kg of U50,488H inhibited bladder sensitivity. However, when animals received bladder inflammation both EIL and as adults, 1 mg/kg of U50,488H increased bladder sensitivity. 4 mg/kg of U50,488H inhibited bladder sensitivity in all animals, but to a lesser extent in animals that received inflammation both EIL and as adults. In Experiment 2, spinal cord, serum, and bladder content of dynorphin were measured using enzyme-linked immunosorbent assay (ELISA). EIL bladder inflammation increased dynorphin content in the lumbosacral spinal cord. In contrast, EIL bladder inflammation and adult re-inflammation decreased bladder content of dynorphin relative to animals that received EIL inflammation alone. In Experiment 3, intrathecal (i.t.) administration of the &kappa-opioid receptor antagonist nor-BNI occurred 24 hours prior to U50,488H administration to determine whether the effects of U50,488H were due to a spinal site of action. Animals receiving i.t. saline vehicle had attenuated responses to U50,488H. Therefore, it was difficult to determine if i.t. administration of nor-BNI prevented the effects of U50,488H. In conclusion, EIL bladder inflammation followed by adult re-inflammation reduced the inhibitory effect of U50,488H and revealed a facilitatory effect. Changes in spinal and bladder dynorphin content may contribute to this reduction in inhibition. Therefore, alterations in the dynorphin/κ-opioid system may participate in bladder hypersensitivity and impairment of opioid inhibition after EIL inflammation and adult re-inflammation.



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