ASPIRIN AND ACETAMINOPHEN REDUCED BOTH FOS EXPRESSION IN RAT LUMBAR SPINAL-CORD AND INFLAMMATORY SIGNS PRODUCED BY CARRAGEENAN INFLAMMATION

This study, performed in freely moving rats, evaluates the effects of the two most prescribed analgesics, aspirin and acetaminophen, on carr ageenin inflammation and the associated c-Fos expression in the rat lu mbar spinal cord. Maximal dorsal horn c-Fos expression is observed 3 h after carrageenin (6 mg/150 mu l of saline), with Fos-like (Fos-LI) n eurones 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 wit h aspirin (75 or 150 mg/kg, i.v.) reduced the number of Fos-LI neurone s induced by carrageenin-inflammation (28 +/- 2% and 45 +/- 1% reducti on, 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 low er dose (75 mg/kg), the effects of aspirin were significantly more mar ked 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 laminae, these differenti al effects being significant for 75 mg/kg of aspirin (P < 0.01) and 15 0 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 pos itive correlation between the effects of aspirin and acetaminophen on the number of Fos-LI neurones and the inflammatory signs which develop ed after carrageenin. Our results suggest that the effects of both dru gs are mainly due to a peripheral site of action without rejecting an additional central site of action of systemic non-steroidal anti-infla mmatory drugs (NSAIDs) and acetaminophen. In addition, our results sug gest that the approach we used could be a useful tool to evaluate syst ematically and quantitatively the effects of NSAIDs. Finally, the effe cts obtained with the low dose of acetaminophen question the classical view of textbooks claiming that such a compound had no anti-inflammat ory effect and are in agreement with previous observations in humans ( Skjelbred and Lokken 1979; Skjelbred et al. 1984).