J Neurogastroenterol Motil.  2016 Apr;22(2):333-343. 10.5056/jnm15127.

Acute Effects of Transforming Growth Factor-β1 on Neuronal Excitability and Involvement in the Pain of Rats with Chronic Pancreatitis

• Zhang X
• Zheng H
• Zhu HY
• Hu S
• Wang S
• Jiang X
• Xu GY

• KMID: 2203587
• DOI: http://doi.org/10.5056/jnm15127

Abstract

BACKGROUND/AIMS
This study was to investigate whether transforming growth factor-β1 (TGF-β1) plays a role in hyperalgesia in chronic pancreatitis (CP) and the underlying mechanisms.
METHODS
CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into the pancreas was used to label pancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGF-β1 on acutely isolated pancreas-specific DRG neurons. Western blot analysis was carried out to measure the expression of TGF-β1 and its receptors.
RESULTS
TNBS injection significantly upregulated expression of TGF-β1 in the pancreas and DRGs, and TGF-β1 receptors in DRGs (T9-T13) in CP rats. Intrathecal injection of TGF-β receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGF-β1 application depolarized the membrane potential and caused firing activity of DRG neurons. TGF-β1 application also reduced rheobase, hyperpolarized action potential threshold, and increased numbers of action potentials evoked by current injection of pancreas-specific DRG neurons. TGF-β1 application also increased the concentration of intracellular calcium of DRG neurons, which was inhibited by SB431542. Furthermore, intrathecal injection of TGF-β1 produced abdominal hyperalgesia in healthy rats.
CONCLUSIONS
These results suggest that TGF-β1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGF-β1 and its receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.

Keyword

Abdominal pain; Chronic pancreatitis; Dorsal root ganglion; Transforming growth factor beta 1

MeSH Terms

Abdomen
Abdominal Pain
Action Potentials
Adult
Animals
Blotting, Western
Calcium
Diagnosis-Related Groups
Fires
Ganglia, Spinal
Humans
Hyperalgesia
Injections, Spinal
Male
Membrane Potentials
Neurons*
Pancreas
Pancreatitis, Chronic*
Rats*
Calcium