title: Artemin Immunotherapy Is Effective in Preventing and Reversing Cystitis-Induced Bladder Hyperalgesia via TRPA1 Regulation.
abstract: Injury- or disease-induced artemin (ARTN) signaling can sensitize primary afferents and contribute to persistent pain. We demonstrate that administration of an ARTN neutralizing antibody, anti-artemin (α-ARTN), can block the development of, and reverse already established, bladder hyperalgesia associated with cyclophosphamide-induced cystitis in mice. We further demonstrate that α-ARTN therapy blocks upregulation of TRPA1, an ion channel contributing to persistent bladder pain during cyclophosphamide-induced cystitis, and decreases phospho-ERK1/2 immunoreactivity in regions of the spinal cord receiving bladder afferent input. Thus, α-ARTN is a promising novel therapeutic approach for treatment of bladder hyperalgesia that may be associated with interstitial cystitis/painful bladder syndrome, as well as cystitis associated with antitumor or immunosuppressive cyclophosphamide therapy.
  
  
  CONCLUSIONS
  α-ARTN therapy effectively prevented and reversed ongoing bladder hyperalgesia in an animal model of cystitis, indicating its potential as an efficacious treatment strategy for ongoing bladder pain associated with interstitial cystitis/painful bladder syndrome.
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: jenjdeb@uab.edu.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: DeBerry
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jami L
authors.initials: JL
authors.lastname: Saloman
authors.affiliation: Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Dragoo
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Albers
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Davis
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D016009:Chi-Square Distribution; D002772:Cholera Toxin / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity; D003556:Cystitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D059265:Visceral Pain / Q000209:etiology
chemical_list: D000906:Antibodies; D018906:Antineoplastic Agents, Alkylating; C116599:Artn protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D003520:Cyclophosphamide; D002772:Cholera Toxin; D020932:Nerve Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium
keywords: Bladder; TRPA1; artemin; cystitis; growth factor; pain; visceral