Targeting nNOS ameliorates the severe neuropathic pain due to chronic pancreatitis.

ABSTRACT:

Background

Pain due to pancreatic cancer/PCa or chronic pancreatitis/CP, is notoriously resistant to the strongest pain medications. Here, we aimed at deciphering the specific molecular mediators of pain at surgical-stage pancreatic disease and to discover novel translational targets.

Methods

We performed a systematic, quantitative analysis of the neurotransmitter/neuroenzmye profile within intrapancreatic nerves of CP and PCa patients. Ex vivo neuronal cultures treated with human pancreatic extracts, conditional genetically engineered knockout mouse models of PCa and CP, and the cerulein-induced CP model were employed to explore the therapeutic potential of the identified targets.

Findings

We identified a unique enrichment of neuronal nitric-oxide-synthase (nNOS) in

SUBMITTER: Demir IE 

PROVIDER: S-EPMC6711864 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature