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Updated: May 21, 2026
Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Effects of general anesthetics on P2X4 receptors in a mouse microglial cell line
Megumi Hasaka1, Takashi Mori, Tadashi Matsuura
1Department of Anesthesiology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
Abstract:
The purinergic P2X4 receptors (P2X4Rs) of spinal microglia are upregulated after a peripheral nerve injury and play important roles in the pathogenesis of chronic pain. The effects of general anesthetics on chronic pain and the mechanisms are still unclear. The aim of this study is to examine the effects of general anesthetics on microglial P2X4Rs. Currents induced by ATP were recorded by the whole-cell clamp technique using a mouse microglial cell line (MG5). Isoflurane and sevoflurane, ketamine, thiopental, midazolam, and propofol were coapplied with ATP using the U-tube system or added to the external perfusate. ATP-induced two distinct types of current: P2X4R-mediated and P2X7R-mediated currents. P2X4R-mediated currents were identified pharmacologically and isolated. Volatile anesthetics including sevoflurane and isoflurane and intravenous anesthetics including thiopental, ketamine, and midazolam had no effect at clinically relevant concentrations (n=5-8). Propofol showed a dual effect, potentiating at lower concentrations (0.3-3 µM) and inhibiting at higher concentrations (IC50 57 µM). The maximum enhancement was observed at 1 µM propofol (143±5% of control, n=5). Propofol (1 µM) shifted the dose-response curve for the P2X4R currents to lower concentrations of ATP and increased the maximum amplitude. Propofol exerted dual actions on P2X4R-mediated currents at clinically relevant concentrations. This may suggest that the administration of propofol could affect the development of chronic pain through the modulation of microglial P2X4R responses.
Insights
General anesthetics like propofol can affect chronic pain by modulating microglial P2X4 receptors (P2X4Rs). Propofol showed dual effects, potentially impacting pain development.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Spinal microglia P2X4 receptors (P2X4Rs) are upregulated post-nerve injury, contributing to chronic pain.
- The impact of general anesthetics on chronic pain mechanisms, particularly microglial P2X4Rs, remains unclear.
Purpose of the Study:
- To investigate the effects of various general anesthetics on microglial P2X4Rs.
- To elucidate the mechanisms by which anesthetics might influence chronic pain pathways.
Main Methods:
- Whole-cell clamp technique used to record ATP-induced currents in a mouse microglial cell line (MG5).
- Pharmacological isolation and identification of P2X4R-mediated currents.
- Co-application or external perfusion of anesthetics (isoflurane, sevoflurane, ketamine, thiopental, midazolam, propofol) with ATP.
Main Results:
- Volatile anesthetics (sevoflurane, isoflurane) and most intravenous anesthetics (ketamine, thiopental, midazolam) had no significant effect on P2X4R currents at clinical concentrations.
- Propofol exhibited a dual effect: potentiation at low concentrations (0.3-3 µM) and inhibition at high concentrations (IC50 57 µM).
- Low-concentration propofol (1 µM) enhanced P2X4R currents, shifting the dose-response curve and increasing maximum amplitude.
Conclusions:
- Propofol modulates microglial P2X4R activity in a concentration-dependent manner.
- These findings suggest propofol's potential to influence chronic pain development via P2X4R modulation.
- Further research is warranted to explore the clinical implications of propofol's effects on P2X4Rs in chronic pain.
