Antinociceptive effect of lupeol: evidence for a role of cytokines inhibition.

The present study investigates the antinociceptive properties of lupeol in models of inflammatory and post-operative pain, as well as its mechanisms of action. The effects of lupeol were tested against acetic acid-induced writhing, formalin test, carrageenan-induced hyperalgesia, and post-operative pain model. Cytokine levels were determined by ELISA. Mice motor performance was evaluated in the rota rod and open-field tests. Pre-treatment of mice with lupeol (5-100 mg/kg IP) produced a dose-related inhibition of writhing in mice. The maximal antinociception produced by lupeol (60 mg/kg) was unaffected in mice pre-treated with yohimbine (α2 adrenoceptor antagonist; 2 mg/kg IP), L-arginine (substrate for nitric oxide synthase; 600 mg/kg IP), glibenclamide (the KATP-channel blocker; 2 mg/kg IP), and methysergide maleate (serotoninergic receptors antagonist; 5 mg/kg IP). Furthermore, lupeol (25-100 mg/kg) inhibited the late phase of formalin test. Pre-treatment with lupeol (50 and 100 mg/kg) inhibited the hyperalgesia and the local increase in tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels induced by carrageenan. In contrast, lupeol did not inhibit the post-operative pain. Lupeol-treated mice did not show any motor performance alterations or apparent systemic toxicity. Our results demonstrate that lupeol has consistent antinociceptive properties during inflammatory pain, but not post-operative pain, acting through the inhibition of IL-1β and TNF-α production.