» Articles » PMID: 22963239

Transforming Growth Factor Beta Induces Sensory Neuronal Hyperexcitability, and Contributes to Pancreatic Pain and Hyperalgesia in Rats with Chronic Pancreatitis

Overview
Journal Mol Pain
Date 2012 Sep 12
PMID 22963239
Citations 29
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models.

Sankaranarayanan I, Kume M, Mohammed A, Mwirigi J, Inturi N, Munro G bioRxiv. 2024; .

PMID: 39149295 PMC: 11326310. DOI: 10.1101/2024.08.07.606891.


Recent advances in the understanding and management of chronic pancreatitis pain.

Walker J, Babyok O, Saloman J, Evans Phillips A J Pancreatol. 2024; 7(1):35-44.

PMID: 38524856 PMC: 10959534. DOI: 10.1097/JP9.0000000000000163.


NHE3 inhibitor tenapanor maintains intestinal barrier function, decreases visceral hypersensitivity, and attenuates TRPV1 signaling in colonic sensory neurons.

King A, Chang L, Li Q, Liu L, Zhu Y, Pasricha P Am J Physiol Gastrointest Liver Physiol. 2024; 326(5):G543-G554.

PMID: 38252683 PMC: 11376972. DOI: 10.1152/ajpgi.00233.2023.


Serum Biomarkers of Nociceptive and Neuropathic Pain in Chronic Pancreatitis.

Saloman J, Li Y, Stello K, Li W, Li S, Evans Phillips A J Pain. 2023; 24(12):2199-2210.

PMID: 37451493 PMC: 10787046. DOI: 10.1016/j.jpain.2023.07.006.


The Antinociceptive Effect of Sympathetic Block is Mediated by Transforming Growth Factor β in a Mouse Model of Radiculopathy.

Luckemeyer D, Xie W, Prudente A, Qualls K, Tonello R, Strong J Neurosci Bull. 2023; 39(9):1363-1374.

PMID: 37165177 PMC: 10465463. DOI: 10.1007/s12264-023-01062-5.


References
1.
Xu G, Winston J, Shenoy M, Yin H, Pendyala S, Pasricha P . Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. Gastroenterology. 2007; 133(4):1282-92. DOI: 10.1053/j.gastro.2007.06.015. View

2.
Anscher M, Thrasher B, Zgonjanin L, Rabbani Z, Corbley M, Fu K . Small molecular inhibitor of transforming growth factor-beta protects against development of radiation-induced lung injury. Int J Radiat Oncol Biol Phys. 2008; 71(3):829-37. DOI: 10.1016/j.ijrobp.2008.02.046. View

3.
Phuket T, Covarrubias M . Kv4 Channels Underlie the Subthreshold-Operating A-type K-current in Nociceptive Dorsal Root Ganglion Neurons. Front Mol Neurosci. 2009; 2:3. PMC: 2724030. DOI: 10.3389/neuro.02.003.2009. View

4.
Takeda M, Tanimoto T, Nasu M, Matsumoto S . Temporomandibular joint inflammation decreases the voltage-gated K+ channel subtype 1.4-immunoreactivity of trigeminal ganglion neurons in rats. Eur J Pain. 2007; 12(2):189-95. DOI: 10.1016/j.ejpain.2007.04.005. View

5.
Dunlap K . Forskolin prolongs action potential duration and blocks potassium current in embryonic chick sensory neurons. Pflugers Arch. 1985; 403(2):170-4. DOI: 10.1007/BF00584096. View