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Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis.
Gastroenterology. 2007 Oct; 133(4):1282-92.G

Abstract

BACKGROUND & AIMS

The neurobiologic basis of pancreatic hyperalgesia in chronic pancreatitis (CP) is understood poorly and there is a need to identify novel therapeutic targets. Our aim was to study the role of the transient receptor potential vanilloid 1 (TRPV1), a key integrator of noxious stimuli, in the pathogenesis of pancreatic pain in a rat model of CP.

METHODS

CP was induced in rats by intraductal injection of trinitrobenzene sulfonic acid. TRPV1 currents in pancreas-specific DRG neurons were measured using perforated patch-clamp techniques. Reverse-transcription polymerase chain reaction was used to measure mRNA expression of TRPV1 in these neurons after laser capture microdissection. Immunofluorescence and Western blot analysis, using TRPV1-specific antibodies, also were performed. Pancreatic hyperalgesia was assessed by rat's nocifensive behavior to electrical stimulation of the pancreas.

RESULTS

CP was associated with a 4-fold increase in capsaicin-induced current density (P < .02), along with an increase in the proportion of pancreas-specific DRG neurons that responded to capsaicin (52.9% in controls vs 79.0% in CP; P < .05). CP also was associated with a significant increase in TRPV1 expression both at the messenger RNA and protein level in whole thoracic DRGs and pancreas-specific sensory neurons. Systemic administration of the TRPV1 antagonist SB-366791 markedly reduced both visceral pain behavior and referred somatic hyperalgesia in rats with CP, but not in control animals.

CONCLUSIONS

TRPV1 up-regulation and sensitization is a specific molecular mechanism contributing to hyperalgesia in CP and represents a useful target for treating pancreatic hyperalgesia caused by inflammation.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17698068

Citation

Xu, Guang-Yin, et al. "Transient Receptor Potential Vanilloid 1 Mediates Hyperalgesia and Is Up-regulated in Rats With Chronic Pancreatitis." Gastroenterology, vol. 133, no. 4, 2007, pp. 1282-92.
Xu GY, Winston JH, Shenoy M, et al. Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. Gastroenterology. 2007;133(4):1282-92.
Xu, G. Y., Winston, J. H., Shenoy, M., Yin, H., Pendyala, S., & Pasricha, P. J. (2007). Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. Gastroenterology, 133(4), 1282-92.
Xu GY, et al. Transient Receptor Potential Vanilloid 1 Mediates Hyperalgesia and Is Up-regulated in Rats With Chronic Pancreatitis. Gastroenterology. 2007;133(4):1282-92. PubMed PMID: 17698068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. AU - Xu,Guang-Yin, AU - Winston,John H, AU - Shenoy,Mohan, AU - Yin,Huaizhi, AU - Pendyala,Swaroop, AU - Pasricha,Pankaj Jay, Y1 - 2007/06/20/ PY - 2006/09/25/received PY - 2007/05/31/accepted PY - 2007/8/19/pubmed PY - 2007/10/27/medline PY - 2007/8/19/entrez SP - 1282 EP - 92 JF - Gastroenterology JO - Gastroenterology VL - 133 IS - 4 N2 - BACKGROUND & AIMS: The neurobiologic basis of pancreatic hyperalgesia in chronic pancreatitis (CP) is understood poorly and there is a need to identify novel therapeutic targets. Our aim was to study the role of the transient receptor potential vanilloid 1 (TRPV1), a key integrator of noxious stimuli, in the pathogenesis of pancreatic pain in a rat model of CP. METHODS: CP was induced in rats by intraductal injection of trinitrobenzene sulfonic acid. TRPV1 currents in pancreas-specific DRG neurons were measured using perforated patch-clamp techniques. Reverse-transcription polymerase chain reaction was used to measure mRNA expression of TRPV1 in these neurons after laser capture microdissection. Immunofluorescence and Western blot analysis, using TRPV1-specific antibodies, also were performed. Pancreatic hyperalgesia was assessed by rat's nocifensive behavior to electrical stimulation of the pancreas. RESULTS: CP was associated with a 4-fold increase in capsaicin-induced current density (P < .02), along with an increase in the proportion of pancreas-specific DRG neurons that responded to capsaicin (52.9% in controls vs 79.0% in CP; P < .05). CP also was associated with a significant increase in TRPV1 expression both at the messenger RNA and protein level in whole thoracic DRGs and pancreas-specific sensory neurons. Systemic administration of the TRPV1 antagonist SB-366791 markedly reduced both visceral pain behavior and referred somatic hyperalgesia in rats with CP, but not in control animals. CONCLUSIONS: TRPV1 up-regulation and sensitization is a specific molecular mechanism contributing to hyperalgesia in CP and represents a useful target for treating pancreatic hyperalgesia caused by inflammation. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/17698068/Transient_receptor_potential_vanilloid_1_mediates_hyperalgesia_and_is_up_regulated_in_rats_with_chronic_pancreatitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(07)01156-0 DB - PRIME DP - Unbound Medicine ER -