Abstract
Objective: The aim of our study was to compare the anti-nociceptive action of amitriptyline with fluoxetine and evaluation of their probable mechanism of anti-nociceptive action by observing their individual interactions with morphine, naloxone, yohimbine, and ondansetron.Methods: Albino mice weighing 25-35 grams were taken and divided into 12 groups. Group A-Control(distilled water), Group B-amitriptyline 20 mg/kg, Group C-fluoxetine 20 mg/kg, Group D-morphine 5 mg/kg, Group E-amitriptyline 20 mg/kg+ morphine 5 mg/kg, Group F-amitriptyline 20 mg/kg+ naloxone 3 mg/kg, Group G-amitriptyline 20 mg/kg+ yohimbine 2 mg/kg, Group H-amitriptyline 20 mg/kg+ ondansetron 0.1 mg/kg, Group I-fluoxetine 20 mg/kg+morphine 5 mg/kg, Group J-fluoxetine 20 mg/kg+ naloxone 3 mg/kg, Group K-fluoxetine 20 mg/kg+ yohimbine 2 mg/kg and Group L-fluoxetine 20 mg/kg+ ondansetron 0.1 mg/kg. Hot plate method and acetic acid writhing test were used to assess central and peripheral analgesic activity respectively.Results: Both the amitriptyline and fluoxetine-treated animals showed significantly increased reaction time in a hot plate (p<0.05) and a significant decrease in the number of wriths in acetic acid writhing test (p<0.05), when compared with control. Animals in amitriptyline group showed significantly higher reaction time and less number of wriths when compared to fluoxetine group. Morphine increased, while naloxone, yohimbine and ondansetron decreased the reaction time in a hot plate. In the acetic acid writhing test, a number of wriths significantly decreased when co-treated with morphine and increased when co-treated with naloxone, yohimbine and ondansetron.Conclusion: It is concluded that amitriptyline is a better antinociceptive agent than fluoxetine. Their central and peripheral mechanism of antinociception both involve opioidergic, serotonergic and noradrenergic pathway.
Highlights
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage [1]
Amitriptyline was obtained from Himedia Labs, Bangalore. fluoxetine was obtained from Quality Pharma, Dibrugarh. morphine was obtained from Verve healthcare Ltd, Delhi. naloxone was obtained from Neon laboratories Ltd. yohimbine was obtained from himedia Laboratory Pvt
The results are depicted in table 1. Both amitriptyline and fluoxetine-treated mice showed a significant increase in mean reaction time compared to the control group at 20, 60 and 90 min
Summary
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage [1]. Aδ and C fibres carrying pain terminate in the dorsal horn and excite second order neurons to reach thalamus. From these thalamic areas, the signals are transmitted to basal areas of the brain, as well as to the somatosensory cortex [2]. The role of opioidergic pathway is well known Encephalin causes both presynaptic and postsynaptic inhibition of incoming type C and types Aδ pain fibers at their synapse in dorsal horn [2]. Norepinephrine released from descending pathways suppresses pain primarily by acting through α-2 receptors [4]
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