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

Zhu, Y and Colak, T and Shenoy, M and Liu, L and Mehta, K and Pai, R and Zou, B and Xie, XS and Pasricha, PJ (2012) Transforming growth factor beta induces sensory neuronal hyperexcitability, and contributes to pancreatic pain and hyperalgesia in rats with chronic pancreatitis. Molecular Pain, 8.

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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. © 2012 Zhu et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Zhu, Y
Colak, T
Shenoy, M
Liu, L
Mehta, K
Pai, Rrkp18@pitt.eduRKP18
Zou, B
Xie, XS
Pasricha, PJ
Date: 11 September 2012
Date Type: Publication
Journal or Publication Title: Molecular Pain
Volume: 8
DOI or Unique Handle: 10.1186/1744-8069-8-65
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Date Deposited: 29 Nov 2016 21:08
Last Modified: 03 Feb 2019 06:55
URI: http://d-scholarship.pitt.edu/id/eprint/29838

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