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OtherANALGESIA AND DRUGS OF ABUSE

Effects of Intrathecal or Intracerebroventricular Administration of Nonsteroidal Anti-inflammatory Drugs on a C-Fiber Reflex in Rats

Diego Bustamante, Carlos Paeile, Jean-Claude Willer and Daniel Le Bars
Journal of Pharmacology and Experimental Therapeutics June 1997, 281 (3) 1381-1391;
Diego Bustamante
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Carlos Paeile
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Jean-Claude Willer
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Daniel Le Bars
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Abstract

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 times threshold), and recruitment curves were built by varying the stimulus intensity from 0 to 7 times threshold. The intrathecal (i.t.) but not i.c.v. administration of aspirin, indomethacin, ketoprofen and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex. In contrast, saline was ineffective. Regardless of the route of administration, the drugs never produced disturbances in heart rate and/or acid-base equilibrium. When a constant level of stimulation was used, 500 μg of aspirin i.t. induced a blockade of the reflex immediately after the injection, followed by a partial recovery. Indomethacin produced a stable depression, which reached 80 to 90% with an i.t. dose of 500 μg. Ketoprofen and lysine clonixinate produced a more stable effect; the highest doses (500 μg) produced a steady-state depression of approximately 50% for approximately 30 min. When the recruitment curves were built with a range of nociceptive stimulus intensities, all of the drugs except for indomethacin produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without major modifications in the thresholds; indomethacin also induced a significant dose-related increase in the threshold. The orders of potency for both stimulation paradigms with the i.t. route were the same, namely aspirin > indomethacin > lysine clonixinate ≥ ketoprofen. It is concluded that nonsteroidal anti-inflammatory drugs elicit significant antinociceptive effects at a spinal level, which do not depend on the existence of a hyperalgesic or inflammatory state. Such effects were not seen after injections within the lateral ventricle.

Footnotes

  • Send reprint requests to: Dr. D. Le Bars, INSERM U-161, 2, rue d’Alésia, 75014 Paris, France.

  • ↵1 This work was supported by INSERM. D.B. was supported by a fellowship from Roemmers Labs, Argentina.

  • Abbreviations:
    AUC
    area under the curve
    AURC
    area under the recruitment curve
    EMG
    electromyographic
    i.t.
    intrathecal
    NMDA
    N-methyl-d-aspartate
    NSAID
    nonsteroidal anti-inflammatory drug
    • Received October 3, 1996.
    • Accepted February 3, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 281, Issue 3
1 Jun 1997
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OtherANALGESIA AND DRUGS OF ABUSE

Effects of Intrathecal or Intracerebroventricular Administration of Nonsteroidal Anti-inflammatory Drugs on a C-Fiber Reflex in Rats

Diego Bustamante, Carlos Paeile, Jean-Claude Willer and Daniel Le Bars
Journal of Pharmacology and Experimental Therapeutics June 1, 1997, 281 (3) 1381-1391;

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OtherANALGESIA AND DRUGS OF ABUSE

Effects of Intrathecal or Intracerebroventricular Administration of Nonsteroidal Anti-inflammatory Drugs on a C-Fiber Reflex in Rats

Diego Bustamante, Carlos Paeile, Jean-Claude Willer and Daniel Le Bars
Journal of Pharmacology and Experimental Therapeutics June 1, 1997, 281 (3) 1381-1391;
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