Aspirin and acetaminophen reduced both Fos expression in rat lumbar spinal cord and inflammatory signs produced by carrageenin inflammation

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Abstract
This study, performed in freely moving rats, evaluates the effects of the two most prescribed analgesics, aspirin and acetaminophen, on carrageenin inflammation and the associated c-Fos expression in the rat lumbar spinal cord. Maximal dorsal horn c-Fos expression is observed 3 h after carrageenin (6 mg/150 μl of saline), with Fos-like (Fos-LI) neurones being predominantly located in laminae I–II and V–VI (41 ± 3% and 39 ± 5% of the total number of Fos-LI neurones per section for the control group, respectively) of the dorsal horn. Pretreatment with aspirin (75 or 150 mg/kg, i.v.) reduced the number of Fos-LI neurones induced by carrageenin-inflammation (28 ± 2% and 45 ± 1% reduction, respectively; P < 0.001 for both). Acetaminophen (75 or 150 mg/kg, i.v.) reduced the number of Fos-LI neurones (19 ± 1% and 43 ± 1% reduction, respectively; P < 0.001 for both). When considering the lower dose (75 mg/kg), the effects of aspirin were significantly more marked than those of acetaminophen (P < 0.001). There was a tendency for both aspirin and acetaminophen to have a more pronounced effect on the number of Fos-LI neurones located in deeper laminate, these differential effects being significant for 75 mg/kg of aspirin (P < 0.01) and 150 mg/kg of acetaminophen (P < 0.01). Both the two doses of aspirin and acetaminophen greatly reduced the inflammatory signs associated with the intraplantar injection of carrageenin. Furthermore there was a positive correlation between the effects of aspirin and acetaminophen on the number of Fos-LI neurones and the inflammatory signs which developed after carrageenin. Our results suggest that the effects of both drugs are mainly due to a peripheral site of action without rejecting an additional central site of action of systemic non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. In addition, our results suggest that the approach we used could be a useful tool to evaluate systematically and quantitatively the effects of NSAIDs. Finally, the effects obtained with the low dose of acetaminophen question the classical view of textbooks claiming that such a compound had no anti-inflammatory effect and are in agreement with previous observations in humans (Skjelbred and Lökken 1979; Skjelbred et al. 1984).