title: Transforming growth factor beta induces sensory neuronal hyperexcitability, and contributes to pancreatic pain and hyperalgesia in rats with chronic pancreatitis.
abstract: BACKGROUND
  Transforming growth factor beta (TGFβ) is upregulated in chronic inflammation, where it plays a key role in wound healing and promoting fibrosis. However, little is known about the peripheral effects of TGFβ on nociception.
  
  
  METHODS
  We tested the in vitro effects of TGFβ1 on the excitability of dorsal root ganglia (DRG) neurons and the function of potassium (K) channels. We also studied the effects of TGFβ1 infusion on pain responses to noxious electrical stimulation in healthy rats as well as the effects of neutralization of TGFβ1 on evoked pain behaviors in a rat model of chronic pancreatitis.
  
  
  RESULTS
  Exposure to TGFβ1 in vitro increased sensory neuronal excitability, decreased voltage-gated A-type K(+) currents (IA) and downregulated expression of the Kv1.4 (KCNA4) gene. Further TGFβ1 infusion into the naïve rat pancreas in vivo induces hyperalgesia and conversely, neutralization of TGFβ1 attenuates hyperalgesia only in rats with experimental chronic pancreatitis. Paradoxically, TGFβ1 neutralization in naïve rats results in pancreatic hyperalgesia.
  
  
  CONCLUSIONS
  TGFβ1 is an important and complex modulator of sensory neuronal function in chronic inflammation, providing a link between fibrosis and nociception and is a potentially novel target for the treatment of persistent pain associated with chronic pancreatitis.
authors.affiliation: Johns Hopkins Center for Neurogastroenterology, Department of Medicine, Division of Gastroenterology and Hepatology, Baltimore, MD 21205, USA.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Tugba
authors.initials: T
authors.lastname: Colak
authors.forename: Mohan
authors.initials: M
authors.lastname: Shenoy
authors.forename: Liansheng
authors.initials: L
authors.lastname: Liu
authors.forename: Kshama
authors.initials: K
authors.lastname: Mehta
authors.forename: Reetesh
authors.initials: R
authors.lastname: Pai
authors.forename: Bende
authors.initials: B
authors.lastname: Zou
authors.forename: Xinmin Simon
authors.initials: XS
authors.lastname: Xie
authors.forename: Pankaj J
authors.initials: PJ
authors.lastname: Pasricha
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism; D007150:Immunohistochemistry; D051665:Kv1.4 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D008297:Male; D050500:Pancreatitis, Chronic / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D051665:Kv1.4 Potassium Channel; D016212:Transforming Growth Factor beta