title: Blockade of NGF and trk receptors inhibits increased peripheral mechanical sensitivity accompanying cystitis in rats.
abstract: 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.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Simone D
authors.initials: SD
authors.lastname: Guerios
authors.forename: Zun-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Kyle
authors.initials: K
authors.lastname: Boldon
authors.forename: Wade
authors.initials: W
authors.lastname: Bushman
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bjorling
mesh_terms: D000171:Acrolein / Q000633:toxicity; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D003556:Cystitis / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D004333:Drug Administration Routes; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006930:Hyperalgesia / Q000150:complications / Q000517:prevention & control*; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000037:antagonists & inhibitors; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors*; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D017475:Receptors, Nerve Growth Factor; D000171:Acrolein; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D020917:Receptor, trkA