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| 22KS-029 |
The antinociceptive effect and anxiolytic effects of paroxetine and nefopam in the spinal nerve ligation model of mice
울산대학교 의과대학 마취통증의학교실
Introduction
Neuropathic pain is one of the leading causes of chronic pain.
Anxiety symptoms and chronic pain have been reported to be closely related. The Elevated Plus Maze (EPM) test is used to assess anxiety-related behavior in rodent models of CNS disorders. The EPM apparatus consists of a \"+\"-shaped maze elevated above the floor with two oppositely positioned closed arms, two oppositely positioned open arms, and a center area. The preference for being in open arms over closed arms is calculated to measure anxiety-like behavior.
Paroxetine is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, etc.
Nefopam is a centrally acting, non-opioid painkilling medication, that is primarily used to treat moderate to severe pain. Nefopam acts in the brain and spinal cord to relieve pain via novel mechanisms: antinociceptive effects from triple monoamine reuptake inhibition, and antihyperalgesic activity through modulation of glutamatergic transmission.
We investigated the antinociceptive effect and anxiolytic effects of paroxetine and nefopam using spinal nerve ligation model of mice.
Methods
The experiments were conducted in male ICR mice (25-35 g).
To create the neuropathic rat model, the left L5 and L6 spinal nerves were gently isolated and ligated tightly with 6-0 black silk.
The tactile allodynia was measured with von Frey Filaments using the up-down method.
To monitor the anxiety-like behaviors, a custom-built EPM with two transparent closed arms (77 x 7 x 30 cm) and two open arms (77 x 7 x 2 cm) was used. This maze was elevated 70 cm above ground for all tests, and the behavior was video recorded for 10 min.
Group 1 (vFF and EPM) nave mice - vehicle i.p.
Group 2 (vFF and EPM) nave mice - Paroxetine 100 μg i.p.
Group 3 (vFF and EPM) na(vFF and EPM) neuropathic mice - vehicle i.p.
Group 5 (vFF and EPM) neuropathic mice - Paroxetine 100 μg i.p.
Group 6 (vFF and EPM) neuropathic mice - Nefopam 60 μg i.p.
Results
In the neuropathic mice, the time spent in the closed arms significantly increased compared to nantraperitoneal dministration of paroxetine and nefopam markedly increased the time spent in the open arms while decreasing the time spent in the closed arms.
The total arm entries in EPM tests were comparable among the investigated groups of mice, indicating that regular locomotor activity is maintained after paroxetine or nefopam administration. Both naive mice and neuropathic mice treated with vehicles did not show any significant anxiolytic effects.
Conclusions
The intraperitoneally administered paroxetine and nefopam presented significant antinociceptive and anxiolytic effects. The anxiolytic effects may be caused by paroxetine itself and nefo
Neuropathic pain is one of the leading causes of chronic pain.
Anxiety symptoms and chronic pain have been reported to be closely related. The Elevated Plus Maze (EPM) test is used to assess anxiety-related behavior in rodent models of CNS disorders. The EPM apparatus consists of a \"+\"-shaped maze elevated above the floor with two oppositely positioned closed arms, two oppositely positioned open arms, and a center area. The preference for being in open arms over closed arms is calculated to measure anxiety-like behavior.
Paroxetine is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, etc.
Nefopam is a centrally acting, non-opioid painkilling medication, that is primarily used to treat moderate to severe pain. Nefopam acts in the brain and spinal cord to relieve pain via novel mechanisms: antinociceptive effects from triple monoamine reuptake inhibition, and antihyperalgesic activity through modulation of glutamatergic transmission.
We investigated the antinociceptive effect and anxiolytic effects of paroxetine and nefopam using spinal nerve ligation model of mice.
Methods
The experiments were conducted in male ICR mice (25-35 g).
To create the neuropathic rat model, the left L5 and L6 spinal nerves were gently isolated and ligated tightly with 6-0 black silk.
The tactile allodynia was measured with von Frey Filaments using the up-down method.
To monitor the anxiety-like behaviors, a custom-built EPM with two transparent closed arms (77 x 7 x 30 cm) and two open arms (77 x 7 x 2 cm) was used. This maze was elevated 70 cm above ground for all tests, and the behavior was video recorded for 10 min.
Group 1 (vFF and EPM) nave mice - vehicle i.p.
Group 2 (vFF and EPM) nave mice - Paroxetine 100 μg i.p.
Group 3 (vFF and EPM) na(vFF and EPM) neuropathic mice - vehicle i.p.
Group 5 (vFF and EPM) neuropathic mice - Paroxetine 100 μg i.p.
Group 6 (vFF and EPM) neuropathic mice - Nefopam 60 μg i.p.
Results
In the neuropathic mice, the time spent in the closed arms significantly increased compared to nantraperitoneal dministration of paroxetine and nefopam markedly increased the time spent in the open arms while decreasing the time spent in the closed arms.
The total arm entries in EPM tests were comparable among the investigated groups of mice, indicating that regular locomotor activity is maintained after paroxetine or nefopam administration. Both naive mice and neuropathic mice treated with vehicles did not show any significant anxiolytic effects.
Conclusions
The intraperitoneally administered paroxetine and nefopam presented significant antinociceptive and anxiolytic effects. The anxiolytic effects may be caused by paroxetine itself and nefo