Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-alpha) pathways.

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Dal Bo W, Luiz AP, Martins DF, Mazzardo-Martins L, Santos AR

Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-alpha) pathways.

Fundam Clin Pharmacol. 2013 Oct;27(5):517-25. doi: 10.1111/j.1472-8206.2012.01052.x. Epub 2012 Jul 8.

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22775297 [ View in PubMed
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Abstract

Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 +/- 10% and 90 +/- 6% of the acetic acid-induced nociception, with ID(5)(0) values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 +/- 5% with an ID(5)(0) of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 +/- 9%), kainic (acid kainite) (41 +/- 12%), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 +/- 5%), and substance P (SP) (39 +/- 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-alpha, 65 +/- 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-alpha. Thus, eugenol could represent an important compound in the treatment for acute pain.

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