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Blockade of NGF and trk receptors inhibits increased peripheral mechanical sensitivity accompanying cystitis in rats.

Authors: Guerios, SD  Wang, ZY  Boldon, K  Bushman, W  Bjorling, DE 
Citation: Guerios SD, etal., Am J Physiol Regul Integr Comp Physiol. 2008 Jul;295(1):R111-22. doi: 10.1152/ajpregu.00728.2007. Epub 2008 Apr 30.
Pubmed: (View Article at PubMed) PMID:18448607
DOI: Full-text: DOI:10.1152/ajpregu.00728.2007

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 one or three (at 72-h intervals) 400-microl intravesical instillations of 1 mM acrolein. Sensitivity of the hindpaws to mechanical and thermal stimuli was determined before and 4, 24, 48, 72, and 96 h after treatment. Other groups of rats were treated with intravesical or intrathecal k252a [a nonspecific antagonist of tyrosine kinase (trk) receptors, including trkA, the high-affinity receptor for NGF] before the first or third acrolein instillation. Some rats were intraperitoneally injected with specific NGF-neutralizing antiserum or normal serum before acrolein instillation. Acute and subacute cystitis induced mechanical, but not thermal, referred hyperalgesia that was attenuated by intravesical pretreatment with k252a. Systemic treatment with NGF-neutralizing antiserum before 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 by subacute cystitis. These results suggest that the bladder-derived NGF acting via trk receptors at least partially mediates peripheral sensitization to mechanical stimuli associated with acute and subacute acrolein-induced cystitis.


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RGD Object Information
RGD ID: 7242803
Created: 2013-04-23
Species: All species
Last Modified: 2013-04-23
Status: ACTIVE


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