Transforming growth factor beta induces sensory neuronal hyperexcitability, and contributes to pancreatic pain and hyperalgesia in rats with chronic pancreatitis

Yaohui Zhu, Tugba Colak, Mohan Shenoy, Liansheng Liu, Kshama Mehta, Reetesh Pai, Bende Zou, Xinmin S. Xie, Pankaj J. Pasricha

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number65
JournalMolecular Pain
Volume8
DOIs
StatePublished - Sep 11 2012

Keywords

  • Chronic pain
  • Chronic pancreatitis
  • Kv channels
  • Neuronal sensitization
  • Sensory neurons
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

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