Abstract
Our purpose was to investigate brain-derived neurotrophic factor (BDNF) in chronic pancreatitis (CP) in comparison with the normal pancreas and to evaluate its association with pain. By immunohistochemistry, in the normal pancreas BDNF immunoreactivity was moderately present in the cytoplasm of most ductal cells and weakly present in most acinar cells, islet cells, nerve fibers (including perineurium), and ganglia cells. In contrast, in CP intense immunostaining of BDNF was present in most cells of ductular complexes and in the perineurium of enlarged nerves. Moderate immunostaining of BDNF was found in degenerating acinar cells and islet cells. In addition, moderate immunoreactivity of BDNF was also detected in most enlarged nerve fibers and intrinsic pancreatic ganglia cells in CP samples. Western blot analysis also revealed 5.6-fold higher BDNF levels in CP samples (P < 0.01) compared with normal pancreas samples. The expression level of BDNF was positively correlated with pain intensity (P < 0.01) and pain frequency (P < 0.01) of CP patients. Furthermore, there was a significant relationship (r = 0.68, P < 0.01) between the BDNF immunostaining and the global pain scores. BDNF is increased in CP. Its association with pain suggests that it functions as a peripheral and central pain modulator, as reported previously in other inflammatory disorders.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Di Sebastiano P, Friess H, Di Mola FF, Innocenti P, Büchler MW: Mechanisms of pain in chronic pancreatitis. Ann Ital Chir 71:11–16, 2000
Di Sebastiano P, Fink T, Weihe E, Friess H, Innocenti P, Beger HG, Büchler MW: Immune cell infiltration and growthassociated protein 43 expression correlate with pain in chronic pancreatitis. Gastroenterology 112:1648–1655, 1997
Büchler M, Weihe E, Friess H, Malfertheiner P, Bockman E, Müller S, Nohr D, Beger HG: Changes in peptidergic innervation in chronic pancreatitis. Pancreas 7:183–192, 1992
Friess H, Zhu ZW, di Mola FF, Kulli C, Graber HU, Andren-Sandberg A, Zimmermann A, Kore M, Reinshagen M, Büchler MW: Nerve growth factor and its high-affinity receptor in chronic pancreatitis. Ann Surg 230:615–624, 1999
Lai KO, Fu WY, Ip FC, Ip NY: Cloning and expression of a novel neurotrophin, NT-7, from carp. Mol Cell Neurosci 11:64–76, 1998
Friedman WJ, Greene LA: Neurotrophin signaling via Trks and p75. Exp Cell Res 253:131–142, 1999
Mannion RJ, Costigan M, Decosterd I, Amaya F, Ma QP, Holstege JC, Ji RR, Acheson A, Lindsay RM, Wilkinson GA, Woolf CJ: Neurotrophins: Peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity. Proc Natl Acad Sci USA 96:9385–9390, 1999
Mendell LM, Albers KM, Davis BM: Neurotrophins, nociceptors, and pain. Microsc Res Tech 45:252–261, 1999
Oddiah D, Anand P, McMahon SB, Rattray M: Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder. Neuroreport 9:1455–1458, 1998
Shu XQ, Mendell LM: Neurotrophins and hyperalgesia. Proc Natl Acad Sci USA 96:7693–7696, 1999
Lee SL, Kim JK, Kim DS, Cho HJ: Expression of mRNAs encoding full-length and truncated TrkB receptors in rat dorsal root ganglia and spinal cord following peripheral inflammation. Neuroreport 10:2847–2851, 1999
Tonra JR, Curtis R, Wong V, Cliffer KD, Park JS, Timmes A, Nguyen T, Lindsay RM, Acheson A, DiStefano PS: Axotomy upregulates the anterograde transport and expression of brainderived neurotrophic factor by sensory neurons. J Neurosci 18:4374–4383, 1998
Zhu Z, Friess H, diMola FF, Zimmermann A, Graber HU, Korc M, Büchler MW: Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer. J Clin Oncol 17:2419–2428, 1999
Kashiwagi M, Friess H, Uhl W, Berberat P, Abou-Shady M, Martignoni M, Anghelacopoulos SE, Zimmermann A, Büchler MW: Group II and IV phospholipase A(2) are produced in human pancreatic cancer cells and influence prognosis. Gut 45:605–612, 1999
Causing CG, Gloster A, Aloyz R, Bamji SX, Chang E, Fawcett J, Kuchel G, Miller FD: Synaptic innervation density is regulated by neuron-derived BDNF. Neuron 18:257–267, 1997
Sendtner M: Molecular biology of neurotrophic factors. Baillieres Clin Neurol 4:575–591, 1995
Shu XQ, Llinas A, Mendell LM: Effects of trkB and trkC neurotrophin receptor agonists on thermal nociception: A behavioral and electrophysiological study. Pain 80:463–470, 1999
Terenghi G: Peripheral nerve regeneration and neurotrophic factors. J Anat 194:1–14, 1999
Cho HJ, Kim JK, Zhou XF, Rush RA: Increased brain-derived neurotrophic factor immunoreactivity in rat dorsal root ganglia and spinal cord following peripheral inflammation. Brain Res 764:269–272, 1997
Cho HJ, Kim SY, Park MJ, Kim DS, Kim JK, Chu MY: Expression of mRNA for brain-derived neurotrophic factor in the dorsal root ganglion following peripheral inflammation. Brain Res 749:358–362, 1997
Michael GJ, Averill S, Nitkunan A, Rattray M, Bennett DL, Yan Q, Priestley JV: Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkAexpressing dorsal root ganglion cells and in their central terminations within the spinal cord. J Neurosci 17:8476–8490, 1997
Apfel SC, Wright DE, Wiideman AM, Dormia C, Snider WD, Kessler JA: Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system. Mol Cell Neurosci 7:134–142, 1996
Ihse I, Zoucas E, Gyllstedt E, Lillo-Gil R, Andren-Sandberg A: Bilateral thoracoscopic splanchnicectomy: effects on pancreatic pain and function. Ann Surg 23:785–790, 1999
Maher JW, Johlin FC, Pearson D: Thoracoscopic splanchnicectomy for chronic pancreatitis pain. Surgery 120:603–609, 1996
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zhu, ZW., Friess, H., Wang, L. et al. Brain-Derived Neurotrophic Factor (BDNF) Is Upregulated and Associated with Pain in Chronic Pancreatitis. Dig Dis Sci 46, 1633–1639 (2001). https://doi.org/10.1023/A:1010684916863
Issue Date:
DOI: https://doi.org/10.1023/A:1010684916863