Preclinical Characterization of Antinociceptive Effect of Bergamot Essential Oil and of Its Fractions for Rational Translation in Complementary Therapy

Abstract

Bergamot essential oil (BEO) is endowed with consistent and reproducible antinociceptive and anti-allodynic properties when administered via an inhalation route. However, the effects of its main constituents and of its decolored (DEC) and deterpenated (DET) fractions, which are enriched in limonene or in linalool and linalyl acetate, respectively, on spontaneous motor activity related to anxiety and on formalin-induced licking/biting biphasic behavior have never been investigated before. Therefore, the present research aims to characterize the role of BEO components on an experimental pain model that is relevant to clinical translation. Under our present experimental conditions, a paper filter disc soaked with different volumes of the phytocomplex and of its fractions that was applied at the edge of the observation chamber allowed the effects on the spontaneous motor activity and on the formalin-induced nocifensive response in ddY-strain mice to be studied. The present research demonstrated the effects of the DEC fraction of BEO on motor activity and on formalin-induced licking/biting behavior for the first time, proving that limonene is implicated in reduced motor activity and that it is important for the analgesic effect.

Translational Value of the Transdermal Administration of Bergamot Essential Oil and of Its Fractions

“…While all the fractions were equally active to the whole phytocomplex in the early phase, the DEC fraction induced a more marked decrease in the nocifensive behavior represented by the time of licking/biting during the late phase. This is in agreement with findings previously observed for inhalatory administration, under which the highest volume (800 µL) of the DEC fraction was as effective as comparable volumes of the whole BEO [ 31 ], while even the highest volume of the DET fraction resulted less effective [ 31 ]. Moreover, all the constituents, i.e., d -limonene, linalool, and linalyl acetate, were almost equally effective in the early phase, while linalyl acetate was the most active followed by linalool and limonene in the late phase.…”

“…The experiments followed the Ethical Standards for Investigation of Experimental Pain in Animals Guidelines, and they were approved by the Animal Care and Use of Tohoku Medical and Pharmaceutical University Committee from 8 January 2014 for minimizing the suffering of animals and for using the minimum number of animals necessary for reliable results. In agreement with G*power sample size calculation [ 33 ], according to previous studies [ 29 , 31 ], the minimum number of animals to achieve reliable statistically significant results was n = 8 per experiment.…”

“…The analgesic efficacy for inhalatory administration of the whole phytocomplex, of its decolored (DEC) and deterpenated (DET) fractions, and of the main components endowed with pharmacologic activity, i.e. linalool, d -limonene, and lynalil acetate, on formalin-induced licking/biting was previously determined by our group [ 31 ]. BEO inhalation demonstrated a higher analgesic effect than its fractions [ 29 ], but the highest volume (800 µL) of the DEC fraction was as effective as comparable volumes of the whole phytocomplex [ 31 ].…”

“…linalool, d -limonene, and lynalil acetate, on formalin-induced licking/biting was previously determined by our group [ 31 ]. BEO inhalation demonstrated a higher analgesic effect than its fractions [ 29 ], but the highest volume (800 µL) of the DEC fraction was as effective as comparable volumes of the whole phytocomplex [ 31 ]. On the contrary, the DET fraction proved inferior efficacy even at the highest volume [ 31 ].…”

“…BEO inhalation demonstrated a higher analgesic effect than its fractions [ 29 ], but the highest volume (800 µL) of the DEC fraction was as effective as comparable volumes of the whole phytocomplex [ 31 ]. On the contrary, the DET fraction proved inferior efficacy even at the highest volume [ 31 ]. Nanoemulsion of essential oils after topical transdermal administration resulted effective for peripheral and central analgesia in the hot plate test [ 32 ].…”