Pancreatic pain

Moran, Robert A.; James, Theodore W.; Pasricha, Pankaj J.

doi:10.1097/mog.0000000000000204

Cited by 17 publications

(16 citation statements)

References 100 publications

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“…It is characterized by persistent abdominal pain and ultimately impairs the ability to digest food and the production of pancreatic hormones. Pancreatic inflammation involves central and peripheral sensitization (551). Pancreatic peripheral innervation consists of NG and DRG sensory neuron projections that are likely to innervate the duodenum (466,720).…”

Section: F Trpa1 In Diabetes Obesity and Pancreatitismentioning

confidence: 99%

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Talavera

Startek

Alvarez‐Collazo

et al. 2020

Physiological Reviews

271

274

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The transient receptor potential ankyrin (TRPA) channels are Ca2+-permeable nonselective cation channels remarkably conserved through the animal kingdom. Mammals have only one member, TRPA1, which is widely expressed in sensory neurons and in non-neuronal cells (such as epithelial cells and hair cells). TRPA1 owes its name to the presence of 14 ankyrin repeats located in the NH2 terminus of the channel, an unusual structural feature that may be relevant to its interactions with intracellular components. TRPA1 is primarily involved in the detection of an extremely wide variety of exogenous stimuli that may produce cellular damage. This includes a plethora of electrophilic compounds that interact with nucleophilic amino acid residues in the channel and many other chemically unrelated compounds whose only common feature seems to be their ability to partition in the plasma membrane. TRPA1 has been reported to be activated by cold, heat, and mechanical stimuli, and its function is modulated by multiple factors, including Ca2+, trace metals, pH, and reactive oxygen, nitrogen, and carbonyl species. TRPA1 is involved in acute and chronic pain as well as inflammation, plays key roles in the pathophysiology of nearly all organ systems, and is an attractive target for the treatment of related diseases. Here we review the current knowledge about the mammalian TRPA1 channel, linking its unique structure, widely tuned sensory properties, and complex regulation to its roles in multiple pathophysiological conditions.

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Section: F Trpa1 In Diabetes Obesity and Pancreatitismentioning

confidence: 99%

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Talavera

Startek

Alvarez‐Collazo

et al. 2020

Physiological Reviews

271

274

View full text Add to dashboard Cite

show abstract

“…The management of painful CP remains a major challenge because current therapeutic approaches fail to produce satisfactory results. More effective therapies require the discovery of novel targets based on new advances in our understanding of the neurobiology of painful CP[2,3]. Anatomical knowledge indicates that pancreatic sensory information enters the central nervous system via both sympathetic and vagus nerves.…”

Section: Introductionmentioning

confidence: 99%

The nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats

Bai

Chen

Qiu

et al. 2019

WJG

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BACKGROUNDCentral sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP). We hypothesized that the nucleus tractus solitarius (NTS), a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn, plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.AIMTo investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis.METHODSCP was induced by the intraductal injection of trinitrobenzene sulfonic acid (TNBS) in rats. Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay. Neural activation of the NTS was indicated by immunohistochemical staining for Fos. Basic synaptic transmission within the NTS was assessed by electrophysiological recordings. Expression of vesicular glutamate transporters (VGluTs), N-methyl-D-aspartate receptor subtype 2B (NR2B), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subtype 1 (GluR1) was analyzed by immunoblotting. Membrane insertion of NR2B and GluR1 was evaluated by electron microscopy. The regulatory role of the NTS in visceral hypersensitivity was detected via pharmacological approach and chemogenetics in CP rats.RESULTSTNBS treatment significantly increased the number of Fos-expressing neurons within the caudal NTS. The excitatory synaptic transmission was substantially potentiated within the caudal NTS in CP rats (frequency: 5.87 ± 1.12 Hz in CP rats vs 2.55 ± 0.44 Hz in sham rats, P < 0.01; amplitude: 19.60 ± 1.39 pA in CP rats vs 14.71 ± 1.07 pA in sham rats; P < 0.01). CP rats showed upregulated expression of VGluT2, and increased phosphorylation and postsynaptic trafficking of NR2B and GluR1 within the caudal NTS. Blocking excitatory synaptic transmission via the AMPAR antagonist CNQX and the NMDAR antagonist AP-5 microinjection reversed visceral hypersensitivity in CP rats (abdominal withdraw threshold: 7.00 ± 1.02 g in CNQX group, 8.00 ± 0.81 g in AP-5 group and 1.10 ± 0.27 g in saline group, P < 0.001). Inhibiting the excitability of NTS neurons via chemogenetics also significantly attenuated pancreatic hyperalgesia (abdominal withdraw threshold: 13.67 ± 2.55 g in Gi group, 2.00 ± 1.37 g in Gq group, and 2.36 ± 0.67 g in mCherry group, P < 0.01).CONCLUSIONOur findings suggest that enhanced excitatory transmission within the caudal NTS contributes to pancreatic pain and emphasize the NTS as a pivotal hub for the processing of pancreatic afferents, which provide novel insights into the central sensitization of painful CP.

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“…However, pain can also be secondary to pancreatic duct leaks, pancreatic fluid collections, concomitant malignancy, or ductal calculi [18]. Pain can also persist in patients even after obstruction of the pancreatic duct is relieved as patients with chronic pancreatitis have been shown to develop perineural fibrosis and may also develop visceral hypersensitivity and neural sensitization which can result in patients having persistent pain even after a theoretically definitive intervention such as a total pancreatectomy [19][20][21][22][23][24].…”

Section: Clinical Featuresmentioning

confidence: 99%

Treatment of Chronic Obstructive Pancreatitis

Larsen

Kozarek

2020

Gastrointestinal and Pancreatico-Biliary Diseases: Advanced Diagnostic and Therapeutic Endoscopy

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The endoscopic treatment of chronic obstructive pancreatitis is contingent upon the coexistence of pancreatic duct calculi or the upstream complication of ductal disruption, to include pancreatic pseudocyst, pancreatic ascites, or pancreaticoenteric fistula. Treatment presupposes pancreatic sphincterotomy, catheter, or balloon dilation and the placement of one or more PD endoprostheses. Concomitant calculi require removal, often with the help of electrohydraulic, laser, mechanical, or extracorporeal lithotripsy and, at times, drainage of upstream extraductal fluid collections. More recently, self-expandable stents have been

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Pancreatic pain

Cited by 17 publications

References 100 publications

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease

The nucleus tractus solitarius mediates hyperalgesia induced by chronic pancreatitis in rats

Treatment of Chronic Obstructive Pancreatitis

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