Stinus, Louis, Auriacombe, Marc, Tignol, Jean, Limoge, Aimé and Le Moal, Michel. Transcranial electrical stimulation with high frequency intermittent current (Limoge’s) potentiates opiate-induced analgesia: blind studies. Pain. 42(3):351-363, 1990.

CES with high frequency (166 kHz) intermittent current (100 Hz: 2 µS positive and 4 µS negative pulses, 100 mA peak-to-peak current corresponding to 17.5 mA effective current, “Limoge” current) has been used for several years in cardiac, thoracic, abdominal, urological and micro-surgery in France. The main benefits are a reduced requirement for analgesic drugs, especially opiates, and a long-lasting postoperative analgesia. This study confirmed these clinical observations using an Anesthelec MPO3 device with 213 male Sprague-Dawley rats using the tail-flick latency (TFL) test to measure pain threshold. CES was not found to modify the pain threshold in drug-free rats, but it potentiated morphine-induced analgesia (systemic injection). To obtain a maximal effect, the stimulation must be initiated 3 hours before the drug injection and be maintained throughout the duration of its pharmacological action. CES potentiation was found to depend on the dose of the drug, the intensity of the current and the polarity of electrodes. Blind tests of the efficiency of CES on several opiate analgesic drugs currently used in human surgery (morphine, fentanyl, alfentanil and dextromoramide) confirmed these findings. The analgesic effect of these 4 opiates (TFL as % of baseline without or with CES) were respectively: 174%, 306%; 176%, 336%; 160%, 215%; and 267%, 392%. The results were obtained not only after systemic opiate treatment, but also after intracerebroventricular injection of morphine (10 micrograms; analgesic effect 152%, 207% with CES) suggesting that CES potentiation of opiate-induced analgesia is centrally mediated. These findings confirm clinical observations on the potentiation of the analgesic properties of opiates by CES.

Non-quantitative observations indicated that CES did not affect the behavior of the rats. They ate, drank, and slept as well as the control rats. Under 100 mA CES, the rats moved normally in the cages, during handling they seemed reactive, motor strength and movements were not affected, catalepsy and sedation were absent and their tail-flick reaction was vigorous. This observation suggests the asymptomatic nature of CES, which can be applied for several days without causing any adverse reactions.