Nootropic drug nefiracetam and related compounds are used in diseases with learning and
memory deficits. Recent studies have implicated relationships between learning, memory, and
chronic pain. Thus, in the present report, we have studied the effects of
nootropic drug nefiracetam on the thermal and
mechanical hyperalgesia induced by partial sciatic nerve
ligation or
streptozotocin treatment in mice. In the thermal paw withdrawal test, p.o., s.c., i.t., and i.c.v. administration of
nefiracetam dose dependently reversed the
thermal hyperalgesia observed in nerve-injured mice.
Nefiracetam (p.o. and i.t.) also significantly reversed the
thermal hyperalgesia observed in
streptozotocin-induced diabetic mice. In the paw pressure test, p.o. and i.t. administration of
nefiracetam dose dependently reversed the
mechanical hyperalgesia observed in both nerve-injured and diabetic mice. In contrast,
nefiracetam had no effect in
sham-operated or control nondiabetic mice in all paradigms. Among other
pyrrolidine nootropics (p.o.),
aniracetam produced significant
analgesic effects. Other analogs also had some, but not significant,
analgesic effects. Finally,
nefiracetam (p.o.)-induced
analgesia in injured mice was not affected by
opioid antagonist naloxone (s.c., i.t., and i.c.v.) but was dose dependently inhibited by nicotinic antagonist
mecamylamine (i.t. and i.c.v.). The
analgesic effect of i.t.
nefiracetam was also blocked by i.t.
mecamylamine pretreatment. Together, these findings suggest that
nefiracetam, a new member of the
piracetam group of cognition enhancers, could be a good therapeutic tool against
neuropathic pain. We also demonstrate that
nefiracetam-induced
analgesic action was nonopioid in nature and was due to stimulation of nicotinic
cholinergic system at spinal and supraspinal levels.