Involvement of Calmodulin Inhibition in Analgesia Induced With Low Doses of Intrathecal Trifluoperazine Publisher Pubmed



Golbidi S¹ ; Moriuchi H¹ ; Irie T¹ ; Ghafghazi T¹ ; Hajhashemi V¹
Source: Japanese Journal of Pharmacology Published:2002

Abstract

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 μg) showed a biphasic effect in the formalin test; i.e., analgesia at relatively low doses (1, 10 μg) and hyperalgesia at a high dose (100 μg). No analgesic effects were observed after intrathecal injection of sulpiride (1, 10, 100 μg), atropine (0.1, 1, 10 μg), phentolamine (0.1, 1, 10 μg) and brompheniramine (0.1, 1, 10 μg). Meanwhile, intrathecal calmidazolium (10, 50, 250 μg) induced a dose-dependent analgesia. Histamine (1 μg), physostigmine (1 μg), bromocriptine (1 μg) and norepinephrine (1 μg) did not affect trifluoperazine-induced analgesia. Calcium (20 μg) 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.