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.