Preclinical evidence for rational use of bergamot essential oil in pain trials

The essential oil (EO) of bergamot is used in aromatherapy to minimize stress-induced anxiety, mood disorders and chronic pain. Preclinical data show that for systemic administration bergamot EO is endowed with behavioural and EEG effects being a functional reflection of the phytocomplex interfering with synaptic plasticity (see Bagetta et al., 2010, Fitoterapia 81, 453 – 461). Here we now report experimental evidence demonstrating that bergamot EO is effective in controlling neuropathic pain. Peripheral nerve damage causes neuropathic pain manifested by hyperalgesia and allodynia. Bergamot EO (1 ml/kg s.c. given once daily/7 days) attenuates mechanical allodynia in the spinal nerve ligation model of neuropathic pain in mice (n = 10; p < 0.05 vs. control) and this has been attributed, at least in part, to the anti-inflammatory action of linalool at the spinal level. In partial sciatic nerve injury model, injection of this EO in the injured paw (20 µg; n = 10) induces a local anti-allodynic effect (p < 0.01 vs. control); administration of the EO in the controlateral hindpaw does not attenuate nociceptive response. Similar results are observed after local injection of linalool (10 µg/paw; n = 10) though the effect induced by the monoterpene is longer lasting. Neuropathic pain is often resistant to opioids and neither systemic nor i.t. morphine is effective. In mice, a large dose of morphine (256 µg) is required to achieve an anti-allodynic effect similar to that obtained with a much lower dose in the nociceptive, capsaicin test. In neuropathic mice, intraplantar injection of very low doses of morphine (4.0 – 64 µg) induces a dose-dependent analgesic effect when combined with inactive doses of bergamot EO (5.0 µg) or linalool (2.5 µg). The latter originates from interactions with primary afferent neurons and is important since unwanted side effects in the CNS are avoided. In conclusion, our data form the rational basis for translation of EO of bergamot in pain clinical trials.