Antinociceptive proprieties of bergamot essential oil (BEO)

Several essential oils and natural substances have important anti-inflammatory and analgesic proprieties. Among these, the essential oil of Bergamot (BEO, from Citrus Bergamia, Risso) has been shown from our previous works to interfere with synaptic mechanisms such as neurotransmitter release (Morrone et al., 2007) and to be neuroprotective both in vitro (Corasaniti et al., 2007) and in vivo (Amantea et al., 2009). We further investigated BEO proprieties by studying its effects on nociceptive behaviour in experimental models of pain. To this aim, we used the spinal nerve ligation (SNL) model (Kim & Chung, 1992) and the formalin test as models of neuropathic and inflammatory pain, respectively. Male C57BL/6 mice, that had underwent SNL, were administered BEO (1ml/Kg; s.c.) in a single daily injection, 1 hour before surgery and then once daily for 14 days. The Von Frey’s and Haregreaves’test were then used to assess mechanical and thermal sensitivity up to 28 days after SNL. In the formalin test, mice received a subcutaneous BEO injection 15 minute before the subcutaneous administration of formalin (s.c., 5%, 20 μl) either in the hind paw or on the scruff of the neck. Licking/biting behaviour was then monitored at intervals of 5 min for the following 60min. In the formalin test, BEO modified either one or both phases of the liking/biting behaviour test depending on the dose and on the way of administration used. In particular, BEO administered intraplantarly significantly reduced the first phase of liking/biking behaviour with no effect on the second phase. Instead, the same dose of BEO administered subcutaneously in the scruff of the neck reduced both the first and the second phase of this inflammatory pain model. The subcutaneous administration of a lower dose in the scruff of the neck showed anti-nociceptive effect on the second but not on the first phase of the test. Following SNL, a robust mechanical allodynia developed and lasted over weeks. A daily dose of BEO (1 ml/kg s.c.) administered daily for 7 days attenuated mechanical allodynia compared to SNL vehicle-treated animals. Altogether, our data suggest that BEO is able to interfere with pain sensitivity possibly acting via two different mechanisms (peripheral and central) and may be a useful adjuvant drug for pain treatment (Bagetta et al., 2010). However, BEO toxic profile on cell survival and proliferation suggest a cautionary approach to the use of inappropriate dilutions of the oil (Berliocchi et al., 2011)