OBJECTIVE: To investigate the effects of low (10 Hz) and high-frequency (130 Hz) transcutaneous electrical nerve stimulation (TENS) applied to inflamed paws of rats following chronic treatment with morphine. METHOD: 140 female Holtzman rats were utilized. Carrageenan (250 µg/0.1 ml) was administered to the right hind paws to induce inflammation. Two and a half hours after carrageenan injection, low and high frequency TENS was applied to the inflamed paw for 20 min, and its effect was measured via the Randall-Selitto method. The opioid antagonist naltrexone (3.0 mg/kg, subcutaneously) was administered 30 min before TENS, to verify the release of endogenous opioids. Morphine tolerance (10 mg/kg, subcutaneously) was induced by twice-daily injection over seven days. Low and high frequency TENS treatment was carried out on the eighth day, 2.5 hours after carrageenan injection. Statistical analysis was performed using one-way analysis of variance (ANOVA), followed by the post hoc Bonferroni test, with a significance level of p < 0.05. RESULTS: Both low and high frequency produced 100% inhibition of carrageenan-induced hyperalgesia. Naltrexone-treated animals showed complete reversion of analgesia induced by low but not high-frequency TENS. After attaining morphine tolerance, the low-frequency TENS values indicated complete absence of analgesia, whereas high-frequency TENS induced anti-hyperalgesia. CONCLUSION: The analgesic activity of low-frequency TENS is reduced following the development of morphine tolerance.
TENS,; pain; morphine; tolerance; carrageenan; electrotherapy
