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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.

Authors: Frias, B  Allen, S  Dawbarn, D  Charrua, A  Cruz, F  Cruz, CD 
Citation: Frias B, etal., Neuroscience. 2013 Mar 27;234:88-102. doi: 10.1016/j.neuroscience.2012.12.044. Epub 2013 Jan 8.
Pubmed: (View Article at PubMed) PMID:23313710
DOI: Full-text: DOI:10.1016/j.neuroscience.2012.12.044

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.


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RGD Object Information
RGD ID: 8655857
Created: 2014-05-21
Species: All species
Last Modified: 2014-05-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.