Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis

Guang Yin Xu, John Winston, Mohan Shenoy, Huaizhi Yin, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Chronic pancreatitis (CP) is a relatively common disorder, characterized by glandular insufficiency and chronic, often intractable, pain. The mechanism of pain in CP is poorly understood. We have previously developed a model of trinitrobenzene sulphonic acid (TNBS)-induced CP that results in nociceptive sensitization in rats. This study was designed to examine changes in the excitability and alteration of voltage-gated K+ currents of dorsal root ganglia (DRG) neurons innervating the pancreas. CP was induced in adult rats by an intraductal injection of TNBS. DRG neurons innervating the pancreas were identified by 1,1′-dioleyl-3,3,3′,3-tetramethylindocarbocyanine methanesulfonate fluorescence labeling. Perforated patch-clamp recordings were made from acutely dissociated DRG neurons from control and TNBS-treated rats. Pancreas-specific DRG neurons displayed more depolarized resting potentials in TNBS-treated rats than those in controls (P < 0.02). Some neurons from the TNBS-treated group exhibited spontaneous firings. TNBS-induced CP also resulted in a dramatic reduction in rheobase (P < 0.05) and a significant increase in the number of action potentials evoked at twice rheobase (P < 0.05). Under voltage-clamp conditions, neurons from both groups exhibited transient A-type (IA) and sustained outward rectifier K+ currents (I K). Compared with controls, the average IA but not the average IK density was significantly reduced in the TNBS-treated group (P < 0.05). The steadystate inactivation curve for IA was displaced by ∼20 mV to more hyperpolarized levels after the TNBS treatment. These data suggest that TNBS treatment increases the excitability of pancreas-specific DRG neurons by suppressing IA density, thus identifying for the first time a specific molecular mechanism underlying chronic visceral pain and sensitization in CP.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume291
Issue number3
DOIs
StatePublished - 2006

Fingerprint

Trinitrobenzenes
Afferent Neurons
Sulfonic Acids
Chronic Pancreatitis
Pancreas
Spinal Ganglia
Neurons
Visceral Pain
Intractable Pain
Chronic Pain
Membrane Potentials
Action Potentials
Fluorescence
Pain

Keywords

  • Dorsal root ganglion
  • Inflammation
  • Membrane properties
  • Trinitrobenzene sulfonic acid
  • Visceral pain

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis. / Xu, Guang Yin; Winston, John; Shenoy, Mohan; Yin, Huaizhi; Pasricha, Pankaj Jay.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 291, No. 3, 2006.

Research output: Contribution to journalArticle

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