We examined which of the known properties of
trifluoperazine, including
calmodulin inhibition, are involved in its
analgesic effect. Furthermore, we tried to find any possible interaction between opioidergic system and
calmodulin inhibition-induced
analgesia. Intrathecal
trifluoperazine (1, 10, 100 microg) showed a biphasic effect in the
formalin test; i.e.,
analgesia at relatively low doses (1, 10 microg) and
hyperalgesia at a high dose (100 microg). No
analgesic effects were observed after
intrathecal injection of
sulpiride (1, 10, 100 microg),
atropine (0.1, 1, 10 microg),
phentolamine (0.1, 1, 10 microg) and
brompheniramine (0.1, 1, 10 microg). Meanwhile, intrathecal
calmidazolium (10, 50, 250 microg) induced a dose-dependent
analgesia.
Histamine (1 microg),
physostigmine (1 microg),
bromocriptine (1 microg) and
norepinephrine (1 microg) did not affect
trifluoperazine-induced
analgesia.
Calcium (20 microg) attenuated the antinociceptive effect of
trifluoperazine and inhibited the
analgesic effect of
calmidazolium. Finally,
naloxone (2 mg/kg) decreased
trifluoperazine-induced antinociception but did not have any effects on
calmidazolium-induced
analgesia. We concluded that
calmodulin inhibition may be involved in the
analgesia produced by
trifluoperazine. With increasing doses of
trifluoperazine, the algesic effect seems to overcome the
analgesic effect. It is also suggested that the opioidergic system does not interact with
calmodulin inhibition-induced
analgesia even though this system has a possible role in
trifluoperazine-induced
analgesia.