LOW FREQUENCY, BUT NOT HIGH FREQUENCY, TENS IS LESS EFFECTIVE IN REDUCING HYPERALGESIA IN MORPHINE TOLERANT RATS WITH ARTHRITIS

K A Sluka; B M Taylor; M M McColley; P M Reveiz; M A Judge

PURPOSE: Both TENS and morphine, commonly used for pain relief, have been extensively studied when used independently. However, little literature examines the effectiveness of their combined use. Morphine activates [micro]-opioid receptors and when administered for prolonged periods analgesic tolerance develops. Since TENS also activates opioid receptors (Sluka et al., JPET 289: 840, 1999) it is possible that TENS would be less effective in morphine tolerant subjects. The current study investigated the effectiveness of TENS in the reversal of hyperalgesia in inflamed rats that were morphine tolerant. SUBJECTS: Male Sprague-Dawley rats (225-300g, n=34). METHODS: Morphine tolerance was induced by subcutaneous implantation of morphine pellets over ten days (n=18). Control rats were implanted with placebo pellets (n=16). Knee joint inflammation was induced by injection of 3% kaolin and 3% carrageenan into one knee joint cavity. Secondary heat hyperalgesia was tested as paw withdrawal latency to radiant heat and assessed 1) before pellet implantation, 2) after pellet implantation and before inflammation, 3) after inflammation and 4) after TENS. Animals were randomly assigned to receive no TENS, low frequency or high frequency TENS. TENS was applied to the medial and lateral aspect of the knee joint at a frequency of either 4Hz (low) or 100Hz (high) (electrodes=1mm round pregelled; pulse duration=100 [micro] sec; intensity=sensory; duration=20min). ANALYSIS: Data were converted to percent inhibition of hyperalgesia: (TENS-inflammation)/(baseline-inflammation) (*)100. Differences in percent inhibition between placebo and morphine tolerant groups for animals treated with no TENS, low frequency TENS or high frequency TENS were compared with a one-way ANOVA. RESULTS: In rats receiving placebo pellets, both high and low frequency TENS caused nearly 100% inhibition of secondary hyperalgesia. Percent inhibition of hyperalgesia by low frequency TENS was significantly lower in morphine tolerant rats (33 [+ or -] 11%) compared to placebo rats (106 [+ or -] 35%)(P=0.02). No difference between groups was found in the group that did not receive TENS (P=0.4) or the group that received high frequency TENS (P=0.8). CONCLUSIONS: In morphine tolerant animals, low frequency TENS does not reverse secondary heat hyperalgesia produced by joint inflammation when compared to placebo control animals. Further, high frequency TENS remains effective in morphine tolerant rats. Thus, clinically, patients that are tolerant to morphine should respond best to high frequency TENS. Supported by the Arthritis Foundation. TENS units were donated by EMPI. Morphine and placebo pellets were provided by NIDA.

LOW FREQUENCY, BUT NOT HIGH FREQUENCY, TENS IS LESS EFFECTIVE IN REDUCING HYPERALGESIA IN MORPHINE TOLERANT RATS WITH ARTHRITIS

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