Brain Derived Neurotrophic Factor (BDNF), acting at the spinal cord level, participates in bladder hyperactivity in and referred pain chronic bladder inflammation

Barbara Frias, Shelley J Allen-Birt, David Dawbarn, Ana Charrua, Francisco Cruz, Celia D Cruz

Research output: Contribution to journalArticle (Academic Journal)

Abstract

Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin 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 neurotrophin is the central nervous system, most notably the spinal cord. The effects of centrally‐acting BDNF on bladder function in normal animals or its central role during chronic cystitis are presently unknown, an issue we aimed to clarify in the present study. For that, control non‐inflamed animals received
a single intrathecal injection of BDNF, after which bladder function was evaluated. This treatment caused short‐lasting bladder hyperactivity. Chronic intrathecal administration of BDNF did not affect bladder reflex activity. Cutaneous sensitivity was evaluated as an internal control of BDNF action in both experiments, where we found mechanical allodynia.
To ascertain the role of BDNF in bladder inflammation, animals with cyclophosphamide (CYP)‐induced cystitis received either a general Trk receptor antagonist or a BDNF scavenger via intrathecal injections. 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 ERK phosphorylation, a marker of increased sensory barrage in lumbosacral spinal cord.
Results obtained here indicate that BDNF, acting at the spinal cord level, leads 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.
Original languageEnglish
Pages (from-to)88-102
Number of pages15
JournalBMC Neuroscience
Volume234
Publication statusPublished - 27 Mar 2013

Bibliographical note

I am the leading author from UoB. I have worked in collaboration with this group before and help in design of experiments.

Keywords

  • BDNF TrkB pain interstitial cystitis

Fingerprint Dive into the research topics of 'Brain Derived Neurotrophic Factor (BDNF), acting at the spinal cord level, participates in bladder hyperactivity in and referred pain chronic bladder inflammation'. Together they form a unique fingerprint.

  • Cite this