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Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis.
Am J Physiol Gastrointest Liver Physiol. 2006 Sep; 291(3):G424-31.AJ

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 (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 approximately 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.

Authors+Show Affiliations

Div. of Gastroenterology and Hepatology, Dept. of Internal Medicine, Univ. of Texas Medical Branch, Galveston, Texas 77555, USA. jpasrich@utmb.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16645160

Citation

Xu, Guang-Yin, et al. "Enhanced Excitability and Suppression of A-type K+ Current of Pancreas-specific Afferent Neurons in a Rat Model of Chronic Pancreatitis." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 291, no. 3, 2006, pp. G424-31.
Xu GY, Winston JH, Shenoy M, et al. Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2006;291(3):G424-31.
Xu, G. Y., Winston, J. H., Shenoy, M., Yin, H., & Pasricha, P. J. (2006). Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis. American Journal of Physiology. Gastrointestinal and Liver Physiology, 291(3), G424-31.
Xu GY, et al. Enhanced Excitability and Suppression of A-type K+ Current of Pancreas-specific Afferent Neurons in a Rat Model of Chronic Pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2006;291(3):G424-31. PubMed PMID: 16645160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis. AU - Xu,Guang-Yin, AU - Winston,John H, AU - Shenoy,Mohan, AU - Yin,Huaizhi, AU - Pasricha,Pankaj Jay, Y1 - 2006/04/27/ PY - 2006/4/29/pubmed PY - 2006/9/29/medline PY - 2006/4/29/entrez SP - G424 EP - 31 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 291 IS - 3 N2 - 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 approximately 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. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/16645160/Enhanced_excitability_and_suppression_of_A_type_K+_current_of_pancreas_specific_afferent_neurons_in_a_rat_model_of_chronic_pancreatitis_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00560.2005?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -