The antinociceptive effect of acetylsalicylic acid is differently affected by a CB1 agonist or antagonist and involves the serotonergic system in rats.
OBJECTIVE
Combinations of non-steroidal anti-inflammatory drugs (NSAIDs) and cannabinoids are promising because of their potential synergistic effects in analgesia, resulting in a reduction in dosage and minimizing adverse reactions. The analgesic effect of acetylsalicylic acid (ASA), probably due to a central mechanism, also implicates changes in the central monoaminergic system. Therefore, we decided to evaluate the antinociceptive interaction between the CB(1) receptor agonist, HU210, and ASA in tests involving central pain in rats as well as the implication of the central serotonergic system thereon.


METHODS
The selective CB(1) antagonist SR141716A and the potent cannabinoid agonist HU210 were evaluated alone and in combination with ASA in both algesimetric tests (hot-plate and formalin tests) and for 5-HT activity and 5-HT(2) receptor density and affinity.


RESULTS
ASA or HU210 alone showed a dose-dependent effect in both tests. HU210, at an inactive dose, significantly increased the antinociceptive effect of the sub-active dose of ASA. SR141716A (1.5mg/kgi.p.) was ineffective per se and failed to modify antinociception induced by the HU210 plus ASA combination in either test. HU210 plus ASA significantly decreased the 5-HIAA/5-HT ratio and the 5-HT(2) receptor density in the frontal cortex, changes not antagonized by SR141716A.


CONCLUSIONS
The present study provides evidence that mutual potentiation of the antinociceptive effects of HU210 and ASA may, at least partly, depend on serotonergic mechanisms, with an indirect participation of cannabinodiergic mechanism. In conclusion, combinations of low doses of cannabinoids and NSAIDs may be of interest from the therapeutic point of view.
Sect. of Pharmacology, Dept. of Biomedical Sciences, University of Modena and Reggio Emilia, Modena I-41100, Italy.
Valentina
V
Ruggieri
Giovanni
G
Vitale
Monica
M
Filaferro
Claudio
C
Frigeri
Luigi A
LA
Pini
Maurizio
M
Sandrini
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005625:Frontal Lobe / Q000187:drug effects*; D008297:Male; D010880:Piperidines / Q000819:agonists / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000819:agonists / Q000037:antagonists & inhibitors; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
D000700:Analgesics; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D050486:Serotonin Plasma Membrane Transport Proteins; D001241:Aspirin; D000077285:Rimonabant