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Related Experiment Video

Updated: Jun 27, 2026

Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx

Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx

Published on: May 2, 2025

P2X receptors in sensory neurons co-cultured with cancer cells exhibit a decrease in opioid sensitivity.

I Chizhmakov¹, N Mamenko, T Volkova

¹Bogomoletz Institute of Physiology, Ukraine Bogomoletz Institute of Physiology, Kiev, Ukraine.

The European Journal of Neuroscience

|December 17, 2008

Summary

Cancer cells alter P2X receptor desensitization, reducing opioid effectiveness in pain signaling. This may explain why severe cancer pain is often resistant to opioid treatments.

Related Experiment Videos

Last Updated: Jun 27, 2026

Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx

Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx

Published on: May 2, 2025

Area of Science:

Neuroscience
Molecular Biology
Pain Research

Background:

Opioids modulate P2X receptors in sensory neurons, crucial for persistent pain.
Severe pain, like that from metastatic diseases, is often unresponsive to opioids.

Purpose of the Study:

To investigate if cancer cells influence the sensitivity of P2X(2/3) and P2X(2) receptors to opioids.
To understand mechanisms behind opioid-refractory cancer pain.

Main Methods:

Whole-cell patch-clamp recordings in rat nodose neurons.
Co-culturing neurons with fibrosarcoma cells (NCTC 2472) versus fibroblasts.
Evaluating ATP-activated currents and inhibition by endomorphin-1.

Main Results:

Fibrosarcoma co-culture altered P2X receptor desensitization kinetics.
Opioid (endomorphin-1) inhibition became dependent on response kinetics; 'ultra-slow' responses lost sensitivity.
Prolonged co-culturing increased occurrence of opioid-insensitive responses.
Non-malignant fibroblasts did not induce these changes.

Conclusions:

Fibrosarcoma cells release factors that modify P2X receptor desensitization.
This alteration reduces opioid inhibitory control, potentially contributing to opioid-refractory cancer pain.