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The antinociceptive effect of fluvoxamine
S Schreiber1, M M Backer, J Yanai
1Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Abstract:
The authors conducted a study in order to evaluate the antinociceptive effects of the serotonin-selective reuptake inhibitor (SSRI) antidepressant fluvoxamine and its interaction with various opioid receptor subtypes. Male ICR mice were tested with a hotplate analgesia meter. Fluvoxamine elicited antinociceptive effect in a dose-dependent manner following i.p., i.t. and i.c.v. injection. Naloxone 10 mg/kg s.c. did not abolish the fluvoxamine antinociceptive effect. At the next stage fluvoxamine was administered together with various agonists of opioid receptors. When administered together with opiates, fluvoxamine significantly potentiated analgesia at the kappa(3)-opioid receptor subtype (P < .005) and to a lesser extent, at the mu-, delta-, and kappa(1)-opioid receptors. We conclude that fluvoxamine alone induces an antinociceptive effect. This effect is mediated by non-opioid mechanism of action. These results suggest a potential role for fluvoxamine in the management of pain when co-administered with opioids at low doses.
Insights
The antidepressant fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), demonstrates pain-relieving effects independently. It also enhances analgesia when combined with certain opioid receptor agonists.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Management
Background:
- Selective serotonin reuptake inhibitors (SSRIs) are primarily used for depression.
- The analgesic potential of SSRIs, including fluvoxamine, is an area of ongoing research.
- Understanding the interaction of fluvoxamine with opioid receptors is crucial for pain management strategies.
Purpose of the Study:
- To evaluate the antinociceptive (pain-relieving) effects of fluvoxamine.
- To investigate the interaction between fluvoxamine and different opioid receptor subtypes.
- To determine the mechanism of action underlying fluvoxamine's antinociceptive effects.
Main Methods:
- Antinociceptive effects were assessed in male ICR mice using a hotplate analgesia meter.
- Fluvoxamine was administered via intraperitoneal (i.p.), intrathecal (i.t.), and intracerebroventricular (i.c.v.) routes.
- The effect of naloxone (an opioid antagonist) and co-administration with opioid receptor agonists were examined.
Main Results:
- Fluvoxamine produced a dose-dependent antinociceptive effect across all tested administration routes.
- Naloxone did not inhibit the antinociceptive effect of fluvoxamine, suggesting a non-opioid mechanism.
- Fluvoxamine potentiated analgesia induced by agonists of kappa(3)-, mu-, delta-, and kappa(1)-opioid receptors, most significantly at kappa(3).
Conclusions:
- Fluvoxamine possesses intrinsic antinociceptive properties mediated through a non-opioid pathway.
- Fluvoxamine's ability to potentiate opioid analgesia suggests a potential role in combination pain therapy.
- Low-dose co-administration of fluvoxamine with opioids may offer a novel approach to pain management.