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Brain-derived neurotrophic factor, acting at the spinal cord level, participates in bladder hyperactivity and referred pain during chronic bladder inflammation.

Abstract
Brain-derived neurotrophic factor (BDNF) is a neurotrophin (NT) known to participate in chronic somatic pain. A recent study has indicated that BDNF may participate in chronic cystitis at the peripheral level. However, the principal site of action for this NT is the central nervous system, most notably the spinal cord. The effects of centrally-acting BDNF on bladder function in normal animals and its central role during chronic cystitis are presently unknown. The present study was undertaken to clarify this issue. For that purpose, control non-inflamed animals were intrathecally injected with BDNF, after which bladder function was evaluated. This treatment caused short-lasting bladder hyperactivity; whereas chronic intrathecal administration of BDNF did not elicit this effect. Cutaneous sensitivity was assessed by mechanical allodynia as an internal control of BDNF action. To ascertain the role of BDNF in bladder inflammation, animals with cyclophosphamide-induced cystitis received intrathecal injections of either a general Trk receptor antagonist or a BDNF scavenger. Blockade of Trk receptors or BDNF sequestration notably improved bladder function. In addition, these treatments also reduced referred pain, typically observed in rats with chronic cystitis. Reduction of referred pain was accompanied by a decrease in the spinal levels of extracellular signal-regulated kinase (ERK) phosphorylation, a marker of increased sensory barrage in the lumbosacral spinal cord, and spinal BDNF expression. Results obtained here indicate that BDNF, acting at the spinal cord level, contributes to bladder hyperactivity and referred pain, important hallmarks of chronic cystitis. In addition, these data also support the development of BDNF modulators as putative therapeutic options for the treatment of chronic bladder inflammation.
AuthorsB Frias, S Allen, D Dawbarn, A Charrua, F Cruz, C D Cruz
JournalNeuroscience (Neuroscience) Vol. 234 Pg. 88-102 (Mar 27 2013) ISSN: 1873-7544 [Electronic] United States
PMID23313710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 IBRO. All rights reserved.
Chemical References
  • Brain-Derived Neurotrophic Factor
  • Carbazoles
  • Indole Alkaloids
  • Protein Kinase Inhibitors
  • Cyclophosphamide
  • staurosporine aglycone
  • Receptor, trkB
  • Extracellular Signal-Regulated MAP Kinases
Topics
  • Animals
  • Brain-Derived Neurotrophic Factor (administration & dosage, metabolism, pharmacology, physiology)
  • Carbazoles (pharmacology)
  • Cyclophosphamide
  • Cystitis (chemically induced, metabolism, physiopathology)
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Female
  • Indole Alkaloids (pharmacology)
  • Injections, Spinal
  • Pain, Referred (physiopathology)
  • Protein Kinase Inhibitors (pharmacology)
  • Rats
  • Receptor, trkB (antagonists & inhibitors)
  • Spinal Cord (drug effects, physiopathology)
  • Urinary Bladder (drug effects, physiology, physiopathology)

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