Visceral inflammation, including that arising from bladder inflammation, reduces the threshold to sensation of innocuous or noxious stimuli applied to peripheral structures (referred hyperalgesia). Cystitis may induce transient or persistent plastic changes mediated by neurotrophins, particularly nerve growth factor (NGF), which contribute to increased nociceptive input. In this study, acute or subacute cystitis was induced in female rats by 1 or 3 (given at 72 hour intervals) instillations of acrolein (1mM, 400µl, intravesical). Sensitivity of the hind paws to mechanical and thermal stimuli was determined prior to and 4, 24, 48, 72, and 96 hours after treatment. Other groups of rats were treated with intravesical or intrathecal k252a (a non-specific antagonist of tyrosine kinase receptors, including tyrosine kinase A, the high affinity receptor for NGF) prior to the first or third acrolein instillation. Some rats received intraperitoneal injection of specific NGF neutralizing antiserum or normal serum prior to acrolein instillation. Acute and subacute cystitis induced mechanical, but not thermal, referred hyperalgesia that was attenuated by intravesical pre-treatment with k252a. Systemic treatment NGF neutralizing antiserum prior to instillation of acrolein suppressed subsequent mechanical referred hyperalgesia. Expression of NGF was increased within the bladder by acute or subacute cystitis, and in L6/S1 dorsal root ganglia (DRG) by subacute cystitis. These results suggest that the bladder-derived NGF acting via tyrosine kinase receptors at least partially mediates peripheral sensitization to mechanical stimuli associated with acute and subacute acrolein-induced cystitis.