SYSTEMIC ADMINISTRATION OF CLONIDINE IN COMBINATION WITH TENS PRODUCES AN INCREASED ANTIHYPERALGESIA IN RATS

P Chandran; K A Sluka

PURPOSE: TENS [Alpha]2-adrenoceptor agonists like clonidine produce powerful dose-dependent analgesia in animals and in human subjects and this analgesia is potentiated by opiates. Since TENS works through the release of endogenous opioids, it was hypothesized that administration of an [Alpha]2-adrenoceptor agonist, clonidine, in combination with TENS will produce a greater degree of analgesia. SUBJECTS: Male Sprague Dawley rats (225-300g, n=101). METHODS: Acute inflammation was induced in rats by the subcutaneous injection of 3% carrageenan (0.5 cc) in the plantar surface of one hindpaw. To assess hyperalgesia and effects of treatment, paw withdrawal latency (PWL) (s) to radiant heat applied to the plantar aspect of the paw was measured. Measurements were taken bilaterally before and after induction of inflammation, and after treatment with either clonidine/saline or TENS, or a combination of both. Four hours after induction of inflammation, rats were randomly divided into 6 groups (n=4-11/dose/group): (a) saline + no TENS, (b) saline + low frequency TENS, (c) saline + high frequency TENS, (d) clonidine (0.006-0.2 mg/kg i.p.) + no TENS, (e) clonidine (0.006-0.2 mg/kg i.p.) + low frequency TENS, (f) clonidine (0.006-0.2 mg/kg i.p.) + high frequency TENS. Low (4 Hz) or high (100 Hz) frequency TENS was administered locally to the inflamed paw of the lightly anesthetized animal (1-2% halothane) in conjunction with clonidine or saline. All other parameters were kept constant: pulse width=100 [micro]s, modulation=normal, intensity=2 x motor threshold, duration=20 minutes. Saline control animals were anesthetized but did not receive TENS. ANALYSIS: 2 factor (dose, TENS) repeated measures ANOVA was used to assess changes in PWL followed by Tukey's test to assess differences between groups. RESULTS: Reduced PWL in the inflamed paw following carrageenan injection demonstrates development of primary thermal hyperalgesia (p=0.0001). A significant effect occurred for (a) clonidine dose (p=0.0001), (b) TENS treatment (p=0.0002), and for (c) dose*treatment (p=0.003). The combined doses of clonidine and TENS (both low and high frequency) showed greater increases in PWL when compared to the group that did not receive TENS. CONCLUSIONS: TENS in combination with clonidine enhances the antihyperalgesic effects of TENS alone. Clinically, it may be possible to reduce the dose of clonidine when co-administered with TENS thus reducing side-effects of clonidine and increasing analgesic efficacy of TENS. Supported by the Arthritis Foundation. TENS units donated by EMPI, Inc.

SYSTEMIC ADMINISTRATION OF CLONIDINE IN COMBINATION WITH TENS PRODUCES AN INCREASED ANTIHYPERALGESIA IN RATS

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