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