The Journal of Pain
Volume 11, Issue 3 , Pages 247-255, March 2010

Neonatal Bladder Inflammation Produces Functional Changes and Alters Neuropeptide Content in Bladders of Adult Female Rats

  • Jennifer DeBerry

      Affiliations

    • Department of Psychology, University of Alabama at Birmingham
    • ,
  • Alan Randich

      Affiliations

    • Department of Psychology, University of Alabama at Birmingham
    • ,
  • Amber D. Shaffer

      Affiliations

    • Department of Psychology, University of Alabama at Birmingham
    • ,
  • Meredith T. Robbins

      Affiliations

    • Department of Anesthesiology, University of Alabama at Birmingham
    • ,
  • Timothy J. Ness

      Affiliations

    • Department of Anesthesiology, University of Alabama at Birmingham
    • Corresponding Author InformationAddress reprint requests to Dr Timothy J. Ness, Department of Anesthesiology, 901 19th Street South, BMR2-Room 270, Birmingham, AL 35205.

Received 14 April 2009; received in revised form 28 May 2009; accepted 22 July 2009. published online 30 November 2009.

Abstract 

Neonatal bladder inflammation has been demonstrated to produce hypersensitivity to bladder re-inflammation as an adult. The purpose of this study was to investigate the effects of neonatal urinary bladder inflammation on adult bladder function and structure. Female Sprague-Dawley rats were treated on postnatal days 14 to 16 with intravesical zymosan or anesthesia alone. At 12 to 16 weeks of age, micturition frequency and cystometrograms were measured. Similarly treated rats had their bladders removed for measurement of plasma extravasation after intravesical mustard oil, for neuropeptide analysis (calcitonin gene-related peptide or Substance P) or for detailed histological examination. Rats treated with zymosan as neonates exhibited increased micturition frequency, reduced micturition volume thresholds, greater extravasation of Evans blue after intravesical mustard oil administration, and greater total bladder content of calcitonin gene-related peptide and Substance P. In contrast, there were no quantitative histological changes in the thickness, fibrosis, or mast cells of bladder tissue due to neonatal zymosan treatments. Functional changes in urologic systems observed in adulthood, coupled with the increased neuropeptide content and neurogenic plasma extravasation in adult bladders, suggest that the neonatal bladder inflammation treatment enhanced the number, function, and/or neurochemical content of primary afferent neurons. These data support the hypothesis that insults to the urologic system in infancy may contribute to the development of adult bladder hypersensitivity.

Perspective

Inflammation of the bladder early in life in the rat has multiple sequelae, including laboratory measures that suggest an alteration of the neurophysiological substrates related to the bladder. Some painful bladder syndromes in humans have similar characteristics and so may be due to similar mechanisms.

Key words: Developmental, visceral nociception, hyperalgesia, interstitial cystitis

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 Supported by National Institutes of Health grants DK51413, DK073218 and DK078655.

PII: S1526-5900(09)00657-9

doi:10.1016/j.jpain.2009.07.010

The Journal of Pain
Volume 11, Issue 3 , Pages 247-255, March 2010

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