Treating pain due to pancreatic cancer is one of the leading challenges in clinical gastroenterology. The majority of these patients develop pain recurrence or opiate dependence despite endoscopic or surgical interventions.
Scientists at the Technical University of Munich (TUM) have discovered the cause of this phenomenon for the first time. They suggest that a particular neuroenzyme in the body is present in high concentrations in the nerves of the organ.
Scientists examined pancreatic tissue samples from 42 female and male patients with chronic inflammation (chronic pancreatitis) or cancer of the organ (pancreatic carcinoma). The samples were taken from the head region of the organ. Around there, the nerve density is significantly high, and the pancreatic head is thus evacuated for therapeutic reasons. Tissue donations from healthy subjects served as controls in the new investigation.
Scientists determined the levels of the most significant neurotransmitters and neuroenzymes present in the nerves of the pancreas, which are important for correspondence and signal transmission.
Ekin Demir, head of the study, said, “We’ve created a pain mediator profile for this region of the pancreas, which plays a key role in the development and perception of pain. This makes it easy to detect pathological changes.”
Scientists found an increased level of a specific enzyme in the nerves of the pancreatic tissue patient samples examined: neuronal nitric oxide synthetase (nNOS). This protein is responsible for synthesizing the messenger NO, which is also involved in the development of pain. Specifically, NO prompts neuronal hyperactivation by binding to receptors on the neuronal surface.
When scientists added extracts from the patient samples to nerve cell cultures, they found an increased amount of the nNOS enzyme in the cultured nerve cells.
In a well-established mouse model for pancreatic scientists used a particular inhibitor that blocks nNOS. This substance is now endorsed as an exploratory medication; however, it can’t yet be utilized in humans. Demir’s team found that mice receiving the drug were significantly less delicate to contact in the influenced abdominal area than the control animals. This fills in as a pointer of pain perception.
Ekin Demir’s group plans to test the new medication in preliminary preclinical and clinical examinations, with the expectation of possibly utilizing it as an alternative pain treatment for pancreatic patients.
Journal Reference
- Ihsan Ekin Demir, Tobias Heinrich, Dominique G. Carty, Ömer Cemil Saricaoglu, Sarah Klauss, Steffen Teller, Timo Kehl, Carmen Mota Reyes, Elke Tieftrunk, Maria Lazarou, Dorukhan H. Bahceci, Betül Gökcek, Bahar E. Ucurum, Matthias Maak, Kalliope N. Diakopoulos, Marina Lesina, Michael Schemann, Mert Erkan, Achim Krüger, Hana Algül, Helmut Friess, Güralp O. Ceyhan. (2019). Targeting nNOS ameliorates the severe neuropathic pain due to chronic pancreatitis. EBioMedicine, 46, 431-443. DOI: 10.1016/j.ebiom.2019.07.055