Pain in chronic pancreatitis: the role of neuropathic pain mechanisms

Drewes, Asbjørn Mohr; Krarup, Anne Lund; Detlefsen, Sönke; Malmstrøm, Marie Louise; Dimcevski, Georg; Funch‐Jensen, Peter

doi:10.1136/gut.2007.146621

Cited by 151 publications

(129 citation statements)

References 110 publications

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“…34 Although pain in CP would traditionally be classified as inflammatory pain, recent studies pointed to the simultaneous presence of structural changes in axons and ganglia in CP, thus implying the involvement of a concomitant neuropathic component. 35,36,58 Previous studies have determined that the 'inflammatory' and the 'neuropathic' component of pain in CP may not be independent but instead closely linked: The 'neuro-immune crosstalk' through pancreatic neuritis, and changes in intrapancreatic neural plasticity were all associated with the severity of pain experienced by CP patients. 8,10,33,58 In addition, recent studies support the idea that the peripheral immune system and spinal microglia are crucial in the generation of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Ceyhan

Deucker

Demir

et al. 2009

Laboratory Investigation

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The chemokine fractalkine induces migration of inflammatory cells into inflamed tissues, thereby aggravating inflammatory tissue damage and fibrosis. Furthermore, fractalkine increases neuropathic pain through glial activation, which can be diminished by blocking of its receptor, CX3CR1, through neutralizing antibodies. As chronic pancreatitis (CP) is characterized by tissue infiltration of inflammatory cells, fibrosis, pancreatic neuritis and severe pain, the roles of fractalkine and CX3CR1 were investigated in CP (n ¼ 61) and normal pancreas (NP, n ¼ 21) by QRT-PCR, western blot and immunohistochemistry analyses. Their expression correlated with the severity of pancreatic neuritis, fibrosis, intrapancreatic nerve fiber density and hypertrophy, pain, CP duration and with the amount of inflammatory cell infiltrate immuno-positive for CD45 and CD68. To investigate the influence of fractalkine on pancreatic fibrogenesis, human pancreatic stellate cells (hPSCs) were isolated from patients with CP, incubated with fractalkine and then Collagen-1 and a-smooth muscle actin (a-SMA) expressions were measured. CX3CR1, but not fractalkine, mRNA was overexpressed in CP. In contrast, the protein levels of both CX3CR1 and fractalkine were upregulated. Neuro-immunoreactivity for fractalkine and CX3CR1 was strongest in patients suffering from severe pain and pancreatic neuritis. Long-term suffering from CP was noticeably related to increased neural immunoreactivity of fractalkine. Furthermore, fractalkine and CX3CR1 mRNA overexpressions were associated with enhanced lymphocyte and macrophage infiltration. Advanced fibrosis was associated with increased fractalkine expression, whereas in vitro fractalkine had no significant impact on collagen-1 and a-SMA expressions in hPSCs. Therefore, pancreatic fractalkine expression appears to be linked to visceral pain and to the recruitment of inflammatory cells into the pancreatic tissue and nerve fibers, with subsequent pancreatic neuritis. However, pancreatic fibrogenesis is probably indirectly influenced by fractalkine. Taken together, these novel findings suggest that CX3CR1 represents a potential novel therapeutic target to reduce inflammation and modulate pain in CP.

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Section: Discussionmentioning

confidence: 99%

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Ceyhan

Deucker

Demir

et al. 2009

Laboratory Investigation

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“…[7][8][9] Although experts recommend starting with non-narcotic analgesics followed by weak narcotics, using strong opioids is often necessary. Several papers report that opioids are among the best analgesics in the treatment of the pain of pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

Effect of Transdermal Fentanyl Patches on the Motility of the Sphincter of Oddi

Koo

Moon²,

Choi³

et al. 2010

Gut Liver

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Background/Aims: Pain is one of the most troublesome symptoms of pancreatitis. Transdermal fentanyl patches (TFPs) are long-acting analgesics with a reduced risk of dependency. This prospective study evaluated the effect of TFPs on sphincter of Oddi (SO) motility for the management of pain in pancreatitis. Methods: SO manometry (SOM) was performed using triple-lumen catheters anterogradely inserted through the percutaneous transhepatic route during cholangioscopy in 16 patients. The basal pressure, amplitude, and frequency of the SO were assessed before and after applying a TFP at 24 hour at doses of 25 and 12.5μg/hr, respectively. Results: Two of 16 patients receiving a 25μg/hr. TFP were excluded because of adverse side effects (headache and/or nausea). The mean basal pressure, amplitude, and frequency of SOM did not change significantly in the 25μg/hr TFP group (n=4 patients). Parameters of SO function also did not significantly change in the 12.5μg/hr TFP group (n=11 patients). Conclusions: TFPs below a dose of 25μg/hr may not affect the motility of the SO. Administration of TFPs at lower dosages seems to be a safe analgesic treatment for the pain control of patients with pancreatitis without affecting the function of the SO. (Gut Liver 2010;4: 368-372)

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“…Thus, no single remedy for pain relief exists and an optimal pain treatment can only be achieved on the basis of a better understanding of the pain mechanisms underlying pain in the individual patient [2] . While, the focus of pain origin in CP historically has been on the pancreatic gland, assuming pain to originate in the pancreas or its surrounding organs, recent findings indicate that both peripheral and central pain processing are abnormal in CP patients [1,3] . Various mechanisms responsible for the altered pain processing have been proposed, including pancreatic neuropathy and neural remodeling [4,5] , sensitization of neurons in the spinal cord and the brain [6,7] , reorganization of the brain areas involved in visceral pain processing [8] and alterations in descending pain control from the brainstem and other supraspinal structures [9] .…”

Section: Introductionmentioning

confidence: 99%

Electrophysiology as a tool to unravel the origin of pancreatic pain

Lelic

Olesen

Graversen

et al. 2014

WJGP

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Intense abdominal pain is the most common symptom in chronic pancreatitis, but the underlying mechanisms are not completely understood and pain management remains a significant clinical challenge. The focus of pain origin in chronic pancreatitis traditionally has been on the pancreatic gland, assuming pain to originate in the pancreas or its surrounding organs. However, research in the last decade points to abnormal central nervous system pain processing. For this reason, electroencephalography has been receiving increasing attention. In contrast to imaging methods such as functional magnetic resonance imaging and positron emission tomography, electroencephalogram has excellent temporal resolution making it possible to investigate central processing of pain on a millisecond time scale. Moreover, continuously advancing methodology made it possible to explore brain sources responsible for generation of evoked potentials and hence to study brain reorganization due to pain in chronic pancreatitis. The aim of this review is to give an overview of the current methods and findings in electroencephalography as a tool to unravel the origin of pancreatic pain.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Chronic pancreatitis; Electrophysiology; Evoked potentials; Brain source localization; Electroencephalography frequency analysis; Visceral pain; Chronic pain; Pancreatic pain Core tip: Chronic pancreatitis (CP) is a disease with progressive destruction of the pancreatic gland and intense abdominal pain is one of its main characteristics. The understanding of pain in CP has conventionally focused on the diseased pancreas itself, assuming pain to be due to increased parenchymal or ductal pressure. However, recent research points to possible involvement of abnormal central nervous system pain processing. This review gives an insight into electrophysiology as a tool to unravel brain abnormalities underlying pancreatic pain and provides up to date electrophysiological results in this patient group.

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Pain in chronic pancreatitis: the role of neuropathic pain mechanisms

Cited by 151 publications

References 110 publications

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Effect of Transdermal Fentanyl Patches on the Motility of the Sphincter of Oddi

Electrophysiology as a tool to unravel the origin of pancreatic pain

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