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Updated: Jun 28, 2025
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Published on: October 4, 2022
5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC
Weiwei Fan1, Xijia Yang1, Liang Zhou1
1Xi'an Gaoxin Hospital - Department of General Surgery - Xi'an - China.
Purpose:
Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain.
Methods:
Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106 in a 20 μL suspension) into the pancreas and formed a 2-3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction.
Results:
There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice.
Conclusions:
Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.
Insights
A 5HT2A antagonist improved survival and reduced pain in mice with pancreatic cancer. This suggests targeting the 5HT2A receptor may help manage cancer-related neuropathic pain.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- Pancreatic cancer is a severe source of pain with limited treatment options.
- Cancer-associated pain significantly impacts patient quality of life.
Purpose of the Study:
- To evaluate the therapeutic effect of a 5HT2A antagonist on pancreatic cancer-associated pain.
- To investigate the role of 5HT2A in mediating pain in pancreatic cancer models.
Main Methods:
- Pancreatic cancer was induced in BALB/c-nu mice using SW 1,990 cells.
- Pain behaviors, survival rates, and body weight were monitored.
- Spinal tissue analysis included quantitative real-time PCR for inflammatory mediators and HDAC2.
Main Results:
- 5HT2A antagonist treatment improved survival and body weight compared to the pancreatic cancer group.
- The antagonist significantly ameliorated pain behaviors in mice.
- Reduced mRNA expression of HDAC2 and inflammatory cytokines was observed in the spinal tissue.
Conclusions:
- 5HT2A antagonist effectively alleviates pancreatic cancer pain through HDAC inhibition and modulation of inflammatory cytokines.
- Targeting the 5HT2A receptor shows potential for clinical application in managing neuropathic pain in pancreatic cancer patients.
