Evidence of pancreatic neuropathy and neuropathic pain in hereditary chronic pancreatitis.

Increased neural density and neural hypertrophy are characteristic features of pancreatic neuropathy in chronic pancreatitis. Here, we present the extraordinary case of prominent pancreatic neuropathy in a 21-year-old female patient with hereditary chronic pancreatitis and intractable pain who underwent total pancreatectomy. The histopathological analysis demonstrated remnant pancreatic tissue which was only composed of prominent intrapancreatic nerves and fibrosis, without any visible remaining functional pancreatic parenchyma. These histological alterations, including nerve hypertrophy and increased neural density, are known for different aetiologies of chronic pancreatitis, e.g. alcoholic, idiopathic and tropic pancreatitis. However, this is the first report of a patient with hereditary chronic pancreatitis demonstrating the characteristic features of pancreatic neuropathy and neuropathic pain

Back pain as a potential indicator of local recurrence in pancreatic cancer.

Neural invasion (NI) and severe pain are common features in patients with pancreatic cancer (PCa). Here, we present the case of a 67-year-old patient with PCa whose pre- and postoperative physical situation was clearly dominated by severe pain sensation. The resected pancreas specimen revealed severe and frequent NI by cancer cells. Seven months after R1 resection and additive chemotherapy, the patient presented with severe lumbar back pain. The CT scan showed liver metastasis and local recurrence around the celiac trunk. Yet 1 month after palliative chemotherapy, the patient presented again in poor general condition and lumbar pain requiring constant morphine intake, and died 2 days after hospitalization. Postmortem histological analysis showed local recurrence with an extensive invasion by cancer cells along almost all nerves of the celiac plexus. Hence, new-onset or recurrent back and/or abdominal pain, as in this case, should raise the clinician's suspicion for local recurrence in PCa

The characterization of the activation state of human Schwann cells within pancreatic neuropathy in pancreatic cancer

Das Pankreaskarzinom (PCa) ist durch eine spezifische pankreatische Neuropathie und neuropathische Schmerzen charakterisiert. In der vorliegenden Arbeit konnte erstmalig gezeigt werden, dass die Tumor-Mikroumgebung im PCa eine Aktivierung der peripheren Gliazellen, den Schwannschen Zellen (SZ), induzieren kann. Die Tumorhypoxie induziert hierbei eine Hochregulation der Intermediärfilamente GFAP, Nestin und Vimentin, eine SZ-Hypertrophie und die Sekretion von pro-inflammatorischen Zytokinen aus den SZ. Die Pankreaskarzinomzellen dahingegen steigern die Proliferation von SZ, und T-Lymphozyten potenzieren die Expression von Intermediärfilamenten in den SZ. Die erstmalige Präsentation der SZ-Aktivierung in einer viszeralen Neuropathie bringt entscheidende Erkenntnisse im Rahmen der pankreatischen Neuropathie und des neuropathischen Schmerzsyndroms im PCa.Pancreatic cancer (PCa) is characterized by a specific pancreatic neuropathy and neuropathic pain. The present study demonstrated for the first time that the tumor micro-environment in PCa can induce an activation of peripheral glia cells, Schwann cells (SC). Tumor hypoxia leads to an upregulation of the intermediate filaments GFAP, Nestin and Vimentin, SC hypertrophy and the secretion of proinflammatory cytokines from SC. PCa cells can induce increased proliferation of SC, and T-lymphocytes further boost the expression of intermediate filaments in SC. This seminal demonstration of glial activation in a visceral neuropathy represents a key finding for our understanding of pancreatic neuropathy and neuropathic pain in PCa