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Updated: Aug 18, 2026

Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
Benzodiazepine system is involved in hyperalgesia in rats induced by the exposure to extremely low frequency magnetic
Ji Hoon Jeong1, Kyung Bum Choi, Nam Ju Moon
1Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
Abstract:
Many reports demonstrate that extremely low frequency magnetic fields (ELF MFs, 60 Hz) may be involved in hyperalgesia. In a previous investigation, we suggested that MFs may produce hyperalgesia and such a response may be regulated by the benzodiazepine system. In order to further confirm this effect of MFs, we used diazepam and/or flumazenil with MFs exposure. When testing the pain threshold of rats using hot plate tests, MFs or diazepam (0.5 microg, i.c.v.; a benzodiazepine receptor agonist) induced hyperalgesic effects with the reduction of latency. These effects were blocked by a pretreatment of flumazenil (1.5 mg/kg, i.p.; a benzodiazepine receptor antagonist). When the rats were exposed simultaneously to MFs and diazepam, the latency tended to decrease without statistical significance. The induction of hyperalgesia by co-exposure to MFs and diazepam was also blocked by flumazenil. However, the pretreatment of GABA receptor antagonists such as bicuculline (0.1 microg, i.c.v.; a GABA(A) antagonist) or phaclofen (10 microg, i.c.v.; a GABA(B) antagonist) did not antagonize the hyperalgesic effect of MFs. These results suggest that the benzodiazepine system may be involved in MFs-induced hyperalgesia.
Insights
Extremely low frequency magnetic fields (ELF MFs) may cause hyperalgesia, a heightened pain response. This effect appears regulated by the benzodiazepine system, as shown by blocking with flumazenil.
Area of Science:
- Neuroscience
- Environmental Health
Background:
- Extremely low frequency magnetic fields (ELF MFs) are increasingly reported to be involved in hyperalgesia.
- Previous research suggested a link between MFs and hyperalgesia, potentially mediated by the benzodiazepine system.
Purpose of the Study:
- To further investigate the role of the benzodiazepine system in MFs-induced hyperalgesia.
- To confirm the effect of MFs on pain thresholds and the involvement of specific receptor systems.
Main Methods:
- Rats were exposed to ELF MFs (60 Hz) and/or diazepam (a benzodiazepine receptor agonist).
- Pain thresholds were assessed using the hot plate test, measuring latency.
- Flumazenil (a benzodiazepine receptor antagonist) and GABA receptor antagonists (bicuculline, phaclofen) were used to block or antagonize effects.
Main Results:
- Both MFs and diazepam significantly reduced latency, indicating hyperalgesia.
- Flumazenil pretreatment blocked the hyperalgesic effects of both MFs and diazepam.
- GABA receptor antagonists did not affect MFs-induced hyperalgesia.
Conclusions:
- The benzodiazepine system appears to play a significant role in mediating hyperalgesia induced by ELF MFs.
- MFs-induced hyperalgesia is likely independent of GABA(A) and GABA(B) receptors.

