ArticlePain2026
Mast cell corticotropin-releasing factor receptor 1 contributes to pancreatic cancer pain via mitogen-activated protein kinase/sphingosine kinases type 1 signaling.
Article in Pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
abstractPancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer often accompanied by persistent abdominal pain and stress, significantly compromising patients' quality of life. Previous studies have identified mast cells as crucial contributors to pancreatic cancer-related pain. This study aimed to investigate the role of the mast cell receptor corticotropin-releasing factor receptor 1 (CRFR1) and delineate its underlying mechanisms in mediating pancreatic pain. In the current study, we demonstrated that painful patients with PDAC exhibited markedly increased mast cell infiltration in peritumoral tissues, but not in tumor tissues, along with elevated levels of CRF and mast cell-specific CRFR1 expression, compared to asymptomatic patients. Consistently, in orthotopic PDAC mice models, flow cytometry and immunofluorescence staining confirmed increased CRFR1 expression in mast cells. Both pharmacological inhibition of CRFR1 and mast cell-specific CRFR1 knockout suppressed mast cell degranulation and alleviated cancer pain in male and female mice. Mechanistically, RNA sequencing, western blotting, and enzyme-linked immunosorbent assay indicated that CRFR1 activated mitogen-activated protein kinase (MAPK) pathway signaling, upregulated sphingosine kinases type 1 (SPHK1) expression, and increased sphingosine-1-phosphate (S1P) levels. A rescue experiment revealed that MAPK inhibition blocked CRFR1-induced SPHK1 upregulation in vitro. Importantly, the SPHK1 inhibitor PF543 reduced abdominal hyperalgesia in mice, whereas this effect was abolished in mast cell deficient mice. Moreover, SPHK1 knockdown by siRNA abolished CRFR1-induced mast cell degranulation. These findings highlight the critical role of mast cell CRFR1 in mediating abdominal hyperalgesia and identify the MAPK/SPHK1/S1P axis as an essential pathway, suggesting that targeting mast cell CRFR1 may be a promising therapeutic strategy for managing pancreatic cancer pain.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.