The role of mast cells in the pathogenesis of pain in chronic pancreatitis
Open accessAbstract
Background: The biological basis of pain in chronic pancreatitis is poorly understood. Mast cells have been implicated in the pathogenesis of pain in other conditions. We hypothesized that mast cells play a role in the pain of chronic pancreatitis. We examined the association of pain with mast cells in autopsy specimens of patients with painful chronic pancreatitis. We explored our hypothesis further using an experimental model of trinitrobenzene sulfonic acid (TNBS) -induced chronic pancreatitis in both wild type (WT) and mast cell deficient mice (MCDM). Methods: Archival tissues with histological diagnoses of chronic pancreatitis were identified and clinical records reviewed for presence or absence of reported pain in humans. Mast cells were counted. The presence of pain was assessed using von Frey Filaments (VFF) to measure abdominal withdrawal responses in both WT and MCDM mice with and without chronic pancreatitis. Results: Humans with painful chronic pancreatitis demonstrated a 3.5-fold increase in pancreatic mast cells as compared with those with painless chronic pancreatitis. WT mice with chronic pancreatitis were significantly more sensitive as assessed by VFF pain testing of the abdomen when compared with MCDM. Conclusion: Humans with painful chronic pancreatitis have an increased number of pancreatic mast cells as compared with those with painless chronic pancreatitis. MCDM are less sensitive to mechanical stimulation of the abdomen after induction of chronic pancreatitis as compared with WT. Mast cells may play an important role in the pathogenesis of pain in chronic pancreatitis.
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Cites
Metcalfe, D. D., Baram, D., & Mekori, Y. A. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.4.1033 · Cited by 1,723 · see citing works
Barbara, G., Stanghellini, V., De Giorgio, R., Cremon, C., Cottrell, G. S., Santini, D., Pasquinelli, G., Morselli-Labate, A. M., Grady, E. F., Bunnett, N. W., et al. (2004) · Gastroenterology · doi:10.1053/j.gastro.2003.11.055 · Cited by 1,475 · see citing works
Chuang, H.-H., Prescott, E. D., Kong, H., Shields, S. D., Jordt, S. E., Basbaum, A. I., Chao, M. V., & Julius, D. J. (2001) · Nature · doi:10.1038/35082088 · Cited by 1,257 · see citing works
Chronic pancreatitis: Diagnosis, classification, and new genetic developments
Etemad, B., & Whitcomb, D. C. (2001) · Gastroenterology · doi:10.1053/gast.2001.22586 · Cited by 1,203 · see citing works
Stead, R. H., Tomioka, M., Quinonez, G. E., Simon, G. T., Felten, S. Y., & Bienenstock, J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.9.2975 · Cited by 554 · see citing works
Mast cells are closely apposed to nerves in the human gastrointestinal mucosa
Stead, R. H., Dixon, M. F., Bramwell, N. H., Riddell, R. H., & Bienenstock, J. (1989) · Gastroenterology · doi:10.1016/0016-5085(89)90627-6 · Cited by 445 · see citing works
A new model of visceral pain and referred hyperalgesia in the mouse
Laird, J. M. A., Martínez‐Caro, L., Garcia-Nicas, E., & Cerveró, F. (2001) · Pain · doi:10.1016/s0304-3959(01)00275-5 · Cited by 351 · see citing works
Neurotrophins and hyperalgesia
Shu, X.-Q., & Mendell, L. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.14.7693 · Cited by 266 · see citing works
Elbadawi, A. (1997) · Urology · doi:10.1016/s0090-4295(99)80329-x · Cited by 200 · see citing works
Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin
Koltzenburg, M., Bennett, D., Shelton, D. L., & McMahon, S. B. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00590.x · Cited by 197 · see citing works
Direct Neurite-Mast Cell Communication In Vitro Occurs Via the Neuropeptide Substance P
Suzuki, R., Furuno, T., McKay, D. M., Wolvers, D. A. W., Teshima, R., Nakanishi, M., & Bienenstock, J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.5.2410 · Cited by 194 · see citing works
Reed, D. E., Barajas‐Lopez, C., Cottrell, G., Velazquez‐Rocha, S., Dery, O., Grady, E. F., Bunnett, N. W., & Vanner, S. J. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.032011 · Cited by 192 · see citing works
The Proteinase-Activated Receptor 2 Is Involved in Nociception
Hoogerwerf, W. A., Zou, L., Shenoy, M. M., Sun, D., Micci, M. A., Lee-Hellmich, H., Xiao, S., Winston, J. H., & Pasricha, P. J. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-22-09036.2001 · Cited by 171 · see citing works
Self-citationNerve Growth Factor and Its High-Affinity Receptor in Chronic Pancreatitis
Frieß, H., Zhu, Z., di Mola, F. F., Kulli, C., Graber, H. U., Andrén‐Sandberg, Å., Zimmermann, A., Korc, M., Reinshagen, M., & Büchler, M. W. (1999) · Annals of Surgery · doi:10.1097/00000658-199911000-00002 · Cited by 166 · see citing works
G protein-dependent activation of mast cell by peptides and basic secretagogues
Ferry, X., Brehin, S., Kamel, R., & Landry, Y. (2002) · Peptides · doi:10.1016/s0196-9781(02)00090-6 · Cited by 150 · see citing works
Interstitial Cystitis: A Neuroimmunoendocrine Disorder <sup>a</sup>
THEOHARIDES, T. C., PANG, X., LETOURNEAU, R., & SANT, G. R. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09601.x · Cited by 139 · see citing works
Hyperalgesia due to nerve damage: role of nerve growth factor
Theodosiou, M., Rush, A. R., Zhou, F. X., Hu, D., Walker, S. J., & Tracey, J. D. (1999) · Pain · doi:10.1016/s0304-3959(99)00018-4 · Cited by 130 · see citing works
Gao, C., Liu, S., Hu, H., Gao, N., Kim, G. Y., Xia, Y. L., & Wood, J. D. (2002) · Gastroenterology · doi:10.1053/gast.2002.36581 · Cited by 106 · see citing works
Mast cells differentially express and release active high molecular weight neurotrophins
Skaper, S. D., Pollock, M., & Facci, L. (2001) · Molecular Brain Research · doi:10.1016/s0169-328x(01)00314-x · Cited by 99 · see citing works
Domain-restricted expression of two glutamic acid decarboxylase genes in midgestation mouse embryos
Katarova, Z., Sekerkov�, G., Prodan, S., Mugnaini, E., & Szab�, G. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000904)424:4 · Cited by 91 · see citing works
Zhang, Y. H., & Nicol, G. D. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.05.042 · Cited by 88 · see citing works
Neuroimmune interactions in guinea pig stomach and small intestine
Liu, S., Hu, H.-Z., Gao, N., Gao, C., Wang, G., Wang, X., Peck, O. C., Kim, G., Gao, X., Xia, Y., et al. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00241.2002 · Cited by 84 · see citing works
Mast cell distribution and activation in chronic pancreatitis
Esposito, I., Friess, H., Каппелер, А., et al. (2001) · Human Pathology · doi:10.1053/hupa.2001.28947 · Cited by 80 · see citing works
Nociception in Persistent Pancreatitis in Rats
Vera–Portocarrero, L. P., Lu, Y. C., & Westlund, K. N. (2003) · Anesthesiology · doi:10.1097/00000542-200302000-00029 · Cited by 77 · see citing works
Hoogerwerf, W. A., Shenoy, M. M., Winston, J. H., Xiao, S., He, Z., & Pasricha, P. J. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.07.002 · Cited by 77 · see citing works
Self-citationPuig‐Diví, V., Molero, X., Salas, A., et al. (1996) · Pancreas · doi:10.1097/00006676-199611000-00012 · Cited by 72 · see citing works
Toward understanding (and management) of painful chronic pancreatitis
DiMagno, E. P. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70031-4 · Cited by 68 · see citing works
Winston, J. H., Toma, H., Shenoy, M. M., He, Z.-J., Zou, L., Xiao, S., Micci, M., & Pasricha, P. J. (2003) · Journal of Pain · doi:10.1016/s1526-5900(03)00636-9 · Cited by 65 · see citing works
Self-citationNicholas, R. S., Winter, J., Wren, P. B., Bergmann, R., & Woolf, C. J. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00706-4 · Cited by 58 · see citing works
Mori, N., Suzuki, R., Furuno, T., McKay, D. M., Wada, M., Teshima, R., Bienenstock, J., & Nakanishi, M. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00050.2002 · Cited by 46 · see citing works
Effects of prolonged exposure to histamine on guinea pig intestinal neurons
Tamura, K., & Wood, J. D. (1992) · Digestive Diseases and Sciences · doi:10.1007/bf01300291 · Cited by 44 · see citing works
Characterization of c-kit-positive neurons in the dorsal root ganglion of mouse
Hirata, T., Kasugai, T., Morii, E., et al. (1995) · Developmental Brain Research · doi:10.1016/0165-3806(94)00205-e · Cited by 38 · see citing works
Fu, L.-W., Pan, H., & Longhurst, J. C. (1997) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1997.273.6.h2726 · Cited by 34 · see citing works
Mast cell: pivotal player in lethal acute pancreatitis
Braganza, J. M. (2000) · QJM · doi:10.1093/qjmed/93.7.469 · Cited by 27 · see citing works
Peptide YY ameliorates cerulein-induced pancreatic injury in the rat
Tito, J. M., Rudnicki, M., Jones, D. H., et al. (1993) · The American Journal of Surgery · doi:10.1016/s0002-9610(05)80789-5 · Cited by 22 · see citing works
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Braganza, J. M., Lee, S. H., McCloy, R. F., & McMahon, M. J. (2011) · The Lancet · doi:10.1016/s0140-6736(10)61852-1 · Cited by 469 · see citing works
Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis
Anaf, V., Chapron, C., El Nakadi, I., De Moor, V., Simonart, T., & Noël, J.-C. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.03.057 · Cited by 258 · see citing works
- Authors
- Hoogerwerf, W. A., Gondesen, K., Xiao, S.-Y., Winston, J. H., Willis, W. D., & Pasricha, P. J.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Hoogerwerf, Willemijntje A
- Venue
- BMC Gastroenterology
- Published
- 2005-03-03
- Volume
- 5
- Issue
- 1
- Pages
- 8-8
- ISSN
- 1471-230X (ISSN-L)
- PMC
- PMC554992
- OpenAlex
- W2156641627
- Cited by
- 61
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2019: 4 · 2018: 2 · 2017: 8 · 2016: 1 · 2015: 5 · 2014: 2 · 2013: 7 · 2012: 5
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Gastroenterology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK062330, R01-DK-62330-01)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Keywords
- mast cells, chronic pancreatitis, abdominal pain, mast cell-deficient mice, visceral hypersensitivity, mechanical pain sensitivity, pain pathogenesis
- MeSH terms
- Abdomen, Adult, Aged, Animals, Cadaver, Chronic Disease, Female, Hindlimb, Humans, Male, Mast Cells, Mice, Inbred Strains, Middle Aged, Pain, Pancreas, Pancreatitis, Physical Stimulation, Trinitrobenzenesulfonic Acid, Mice
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