title: Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat.
abstract: BACKGROUND
  In humans, inflammation of either the urinary bladder or the distal colon often results in sensory cross-sensitization between these organs. Limited information is known about the mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation of primary afferent pathways may have a role in mediating viscero-visceral cross-organ sensitization.
  
  
  METHODS
  Colonic inflammation was induced by a single dose of tri-nitrobenzene sulfonic acid (TNBS) instilled intracolonically. The histology of the colon and the urinary bladder was examined by hematoxylin and eosin (H&E) stain. The protein expression of transient receptor potential (TRP) ion channel of the vanilloid type 1 (TRPV1) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry and/or western blot. The inter-micturition intervals and the quantity of urine voided were obtained from analysis of cystometrograms.
  
  
  RESULTS
  At 3 days post TNBS treatment, the protein level of TRPV1 was increased by 2-fold (p < 0.05) in the inflamed distal colon when examined with western blot. TRPV1 was mainly expressed in the axonal terminals in submucosal area of the distal colon, and was co-localized with the neural marker PGP9.5. In sensory neurons in the dorsal root ganglia (DRG), BDNF expression was augmented by colonic inflammation examined in the L1 DRG, and was expressed in TRPV1 positive neurons. The elevated level of BDNF in L1 DRG by colonic inflammation was blunted by prolonged pre-treatment of the animals with the neurotoxin resiniferatoxin (RTX). Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus. However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided. The increased bladder activity by colonic inflammation was attenuated by prolonged intraluminal treatment with RTX or treatment with intrathecal BDNF neutralizing antibody.
  
  
  CONCLUSIONS
  Acute colonic inflammation increases bladder activity without affecting bladder morphology. Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.
authors.affiliation: Department of Physiology, Virginia Commonwealth University School of Medicine, 1220 East Broad Street, PO Box 0551, MMRB 5038, VA 23219 Richmond, Virginia, USA.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Xia
authors.forename: Melisa A
authors.initials: MA
authors.lastname: Gulick
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Yu
authors.forename: John R
authors.initials: JR
authors.lastname: Grider
authors.forename: Karnam S
authors.initials: KS
authors.lastname: Murthy
authors.forename: John F
authors.initials: JF
authors.lastname: Kuemmerle
authors.forename: Hamid I
authors.initials: HI
authors.lastname: Akbarali
authors.forename: Li-Ya
authors.initials: LY
authors.lastname: Qiao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D005727:Ganglia, Spinal / Q000473:pathology; D008297:Male; D009498:Neurotoxins / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014554:Urination / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D019208:Brain-Derived Neurotrophic Factor; D004224:Diterpenes; D009498:Neurotoxins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C019277:brain-derived growth factor; D014302:Trinitrobenzenesulfonic Acid; C024353:resiniferatoxin; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase