Evaluation of the analgesic effect of nabilone versus acetaminophen plus caffeine in an inflammatory pain model (tail flik test) in rats.

Nabilone is a synthetic cannabinoid with a potent agonist effect on CB1 cannabinoid receptors, involved in the regulation of nausea, vomiting, appetite, movement and pain. Several clinical trials confirm the effectiveness of nabilone in treating anxiety and pain associated with fibromyalgia or multiple sclerosis. Nabilone, in man, shows its analgesic/anti-inflammatory activity, and its modulation of allodynia without having significant psychotropic effects. Modification of endogenous cannabinoid (anandamide) has been found in animal model of pain, inflammation and neurological disease. Anandamide and cannabidiol are weak agonists of TPRV1 receptors, normally activated by noxious physical/thermal stimuli or by inflammatory hyperalgesia. The aim of our study was to evaluate the effect of Nabilone and combination of acetaminophen plus caffeine in acute and chronic treatment on hyperalgesia induced by nitro-glycerine (NTG), using tail flick test, in rats. We choose nitro-glycerine as nitric oxide (NO) donor; infusion of NO induces delayed headache in migraineurs and activity of neurons in the spinal trigeminal nucleus. Method 12 Adult male Wistar rats (weight range: 180-355 g) were treated, in acute, with nabilone (2,5 mg/kg p.o.), acetaminophen plus caffeine (400 mg/Kg p.o. + 52 mg/Kg p.o.); and, in chronic (8 days) with nabilone (1 mg/Kg p.o.), acetaminophen plus 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) (18-20 degrees C). Tail flick test was performed during acute treatment, 2-4 hours after injection of NTG; during chronic treatment after a period of 8 days. The test has been conducted with a tail flick 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 beginning of test and the deviation of tail. The highest execution time to avoid tissue damage was 15 sec. Results The treatment with nabilone increased the latency time, during tail flick test vs. controls; in fact the latency time was 15 ± 0.8 sec. (mean ± SD) and 10 ± 0.5 sec. (mean ± SD), respectively in acute and in chronic treatment; rats treated with acetaminophen, 400 or 200 mg/Kg p.o. plus caffeine 52 or 26 mg/kg p.o., respectively, in acute and in chronic administration did not show changes vs. controls (2,7 ± 0.3 sec.; ANOVA and Bonferroni‘ s test; p< 0.05). Conclusion The data supported the efficacy of nabilone in the management of acute and chronic pain. Our main interest was to explore its potential use in the treatment of chronic headache, providing a novel target for an innovative therapeutic approach. Balapal S et al., (2007) Curr Neuropharmacol 5: 81-97 Dieterle A et al., (2011) Cephalalgia 31: 31-42