title: Early-in-life bladder inflammation alters U50,488H but not morphine-induced inhibition of visceromotor responses to urinary bladder distension.
abstract: Previous research has suggested that early-in-life (EIL) exposure to bladder inflammation impairs the function of endogenous opioid inhibitory system(s) and may contribute to the development of chronic bladder pain. This study examined how acute adult and/or prior EIL exposure to bladder inflammation altered the inhibitory effects of systemic κ- and μ-opioid agonists on the visceromotor reflex (VMR) to urinary bladder distension (UBD). Female rats were exposed intravesically EIL (P14-P16) to either the inflammatory agent zymosan or anesthesia-alone, and then rechallenged as adults (12-17 weeks) with either anesthesia-alone or zymosan. The VMR to 60mmHg UBD was measured after cumulative intravenous (i.v.) administration of 1mg/kg and 4mg/kg of either the κ-opioid agonist U50,488H or the μ-opioid agonist morphine. Morphine produced dose-dependent inhibition of the VMR to UBD in all groups, and U50,488H produced dose-dependent inhibition of the VMR to UBD in all but one group. Animals that received bladder inflammation both EIL and as adults showed significantly augmented VMRs to UBD (>100% baseline values) following 1mg/kg of U50,488H and diminished inhibition of VMRs following 4mg/kg of U50,488H when compared with other groups. In contrast, neither EIL nor adult bladder inflammation markedly altered the inhibition of the VMR to UBD produced by either 1 or 4mg/kg of i.v. morphine. These data suggest EIL and adult exposure to bladder inflammation selectively decreases the inhibitory effects of κ-opioids and thereby may enhance bladder hypersensitivity in patients with painful bladder syndromes.
authors.affiliation: University of Alabama at Birmingham, Department of Psychology, CH 415, 1530 3rd Avenue South, Birmingham, AL 35294, USA. shafferad@upmc.edu
authors.forename: Amber D
authors.initials: AD
authors.lastname: Shaffer
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ness
authors.forename: Alan
authors.initials: A
authors.lastname: Randich
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D003556:Cystitis / Q000503:physiopathology*; D004108:Dilatation, Pathologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012018:Reflex / Q000187:drug effects*; D013997:Time Factors; D001743:Urinary Bladder / Q000503:physiopathology*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D015054:Zymosan