Evaluation of the analgesic effect of nabilone versus paracetamolo + caffeine in a model of inflammation, in rats (tail flick test).

M Ciccarese, V Ruggieri, MM Cainazzo, A Ferrari, LA Pini. Univerisity of Modena e Reggio Emilia, Headache and Drug Abuse Inter-Dept Research Centre 41100, Italy

Nabilone is a synthetic cannabinoid with a potent agonist effect on CB1 cannabinoid receptors that are involved in the regulation of nausea, vomiting, appetite, movement and pain. In the recent years, the off-label use of nabilone for chronic pain management has increased. Several clinical trials have confirmed the effectiveness of nabilone in treating anxiety and pain associated with fibromyalgia or multiple sclerosis (1). Nabilone shows its analgesic/anti-inflammatory activity, and its modulation of allodynia without having significant psychotropic effects. CB1 and μ/κ opioid receptors are in the same CNS areas involved in pain control, (PAG), rostral-ventromedial marrow and spinal cord. Changes of endogenous cannabinoid (anandamide) has been found in animal model of pain, inflammation and neurological disease. Anandamide and cannabidiolo are weak agonists of TPRV1 receptors, normally activated by noxious physical/thermal stimuli or by inflammatory hyperalgesia.(2).

The aim of our study is to evaluate the effect of Nabilone and Acetaminophine + caffeine in acute and chronic treatment on hyperalgesia induced by nitroglicerin (NTG), using tail flick test, in rats. We choose nitroglicerin as nitric oxide (NO) donor; NO induces spontaneous-like headache attacks, in migraineurs, and hyperalgesia. Adult male Wistar rats were treated, in acute, with nabilone (2,5 mg/kg p.o.), acetaminophen + caffeine (400 mg/Kg p.o. + 52 mg/Kg p.o.); and, in chronic, (8 days) with nabilone (1 mg/Kg p.o.), acetaminophen + caffeine (200 mg/Kg p.o.+ 26 mg/Kg p.o.), or vehicle, 1 h before the i.p. injection of NTG (10 mg/kg). Tail flick test was made during acute treatment, 2-4 hours after injection of NTG; after a period of 8 days during chronic treatment. The test was conducted with a tail flcik device that use a 375-W movie light focused on the rat’s tail (2-3 cm from the tip) by means of a condenser lens positioned below the light source. The latency time (sec) was evaluated as the time between the beginnings of test and the deviation of tail. The maximun excution time to avoid tissue damage was 15 sec. Acute and chronic treatment with nabilone increased the latency time, during tail flick test vs controls; rats treated with acetaminophene, 400 or 200 mg/kg p.o. + caffeine 52 or 26 mg/kg p.o., respectevely in acute and in chronic administration do not show changes vs controls The data confirm the use of Nabilone in the management of acute and chronic pain. Our main interest is to focalize its use in acute and chronic headache, providing a therapeutic approach that use a novel target and mechanism for pain.