MENTHOL: A NATURAL ANALGESIC COMPOUND

Menthol, after topical application, causes a feeling of coolness due to stimulation of ‘cold’ receptors by inhibiting Ca11 currents of neuronal membranes. Since Ca11 channel blockers are endowed with analgesic properties, the aim of the present study was to investigate the potential antinociceptive effect of menthol. (2)-Menthol produced a dose-dependent increase in the pain threshold in the mouse hot-plate (3–10 mg kg21 p.o.) and abdominal constriction (3–10 mg kg21 p.o.; 10 mg per mouse intracerebroventricularly (i.c.v.)) tests. The antinociceptive effect of (2)-menthol was antagonised by the unselective opioid antagonist naloxone and by the selective k-antagonist nor-NBI. Conversely, CTOP (m-antagonist), 7-benzylidenenal-trexone (d1 antagonist) and naltriben (d2 antagonist) did not prevent (2)-menthol antinociception. In both tests, (1)-menthol (10–50 mg kg21 p.o.; 10–30 mg per mouse i.c.v.) was unable to modify the pain threshold. These results indicate that (2)-menthol is endowed with analgesic properties mediated through a selective activation of kopioid receptors.