Molecular pathway of pancreatic cancer-associated neuropathic pain

Giri S. S., Tripathi A. S., ERKEKOĞLU Ü. P., Zaki M. E. A.

Journal of Biochemical and Molecular Toxicology, vol.38, no.4, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Review
  • Volume: 38 Issue: 4
  • Publication Date: 2024
  • Doi Number: 10.1002/jbt.23638
  • Journal Name: Journal of Biochemical and Molecular Toxicology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Keywords: brain-derived neurotrophic factors (BDNF), mucin 1 (MUC1), myelin-associated glycoprotein (MAG), nerve growth factor (NGF), PDAC neuropathy, perineural invasion, slit guidance ligand 2 (SLIT2), tumor microenvironment
  • Hacettepe University Affiliated: Yes


The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is called pancreatic ductal adenocarcinoma (PDAC). PDAC is the most encountered pancreatic cancer type. One of the most important characteristic features of PDAC is neuropathy which is primarily due to perineural invasion (PNI). PNI develops tumor microenvironment which includes overexpression of fibroblasts cells, macrophages, as well as angiogenesis which can be responsible for neuropathy pain. In tumor microenvironment inactive fibroblasts are converted into an active form that is cancer-associated fibroblasts (CAFs). Neurotrophins they also increase the level of Substance P, calcitonin gene-related peptide which is also involved in pain. Matrix metalloproteases are the zinc-associated proteases enzymes which activates proinflammatory interleukin-1β into its activated form and are responsible for release and activation of Substance P which is responsible for neuropathic pain by transmitting pain signal via dorsal root ganglion. All the molecules and their role in being responsible for neuropathic pain are described below.