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MUCOSAL BIOLOGY

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

Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas

Submitted 13 December 2005 ; accepted in final form 25 April 2006

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 (I_A) and sustained outward rectifier K⁺ currents (I_K). Compared with controls, the average I_A but not the average I_K density was significantly reduced in the TNBS-treated group (P < 0.05). The steady-state inactivation curve for I_A 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 I_A density, thus identifying for the first time a specific molecular mechanism underlying chronic visceral pain and sensitization in CP.

dorsal root ganglion; inflammation; visceral pain; trinitrobenzene sulfonic acid; membrane properties

This article has been cited by other articles:

				A M Drewes, A L Krarup, S Detlefsen, M-L Malmstrom, G Dimcevski, and P Funch-Jensen Pain in chronic pancreatitis: the role of neuropathic pain mechanisms Gut, November 1, 2008; 57(11): 1616 - 1627. [Abstract] [Full Text] [PDF]

				G-Y Xu, M Shenoy, J H Winston, S Mittal, and P J Pasricha P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity Gut, September 1, 2008; 57(9): 1230 - 1237. [Abstract] [Full Text] [PDF]