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Evaluation of the antinociceptive effects of syringic acid in male mice: Using formalin, writhing, and hot plate pain models

Articles in Press

Document Type : Original Article

Authors

1 Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

2 Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Pain Research Center, Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Background: Syringic acid (SA) is a natural phenolic compound with antioxidant and anti-inflammatory properties. Due to limited studies on the analgesic effect of SA, we decided to comprehensively investigate this effect. Thus, the analgesic activity of SA was assessed for the first time using the formalin and writhing models, in addition to the hot plate (HP) test, involving its action on opioid, GABAergic, nitric oxide (NO)/cGMP, and ATP-sensitive K⁺ channel pathways. Furthermore, we examined exploratory and locomotor behaviors post SA administration.
Methods: A total of 231 mice were randomly assigned to groups of 7. SA was administered at doses of 25, 50, and 100 mg/kg. To investigate the possible pathways, naloxone, flumazenil, L-NAME/methylene blue, and glibenclamide were administered before SA injection. Behavioral tests were performed using the open-field (OF) apparatus. Statistical analysis was performed using one-way (or two-way) analysis of variance (ANOVA) with Tukey, least significant difference (LSD), and Bonferroni post hoc tests. All the results were evaluated under blind conditions.
Results: SA showed significant analgesic effects in the acute (P < 0.050) and chronic (P < 0.001) phases of formalin (P < 0.050) and writhing tests (P < 0.001) but not in the HP test. Furthermore, SA decreased exploratory behavior. Opioid receptor blockade reduced the number of writhes (P < 0.050). Moreover, using L-NAME increased the pain reaction time in the HP test (P < 0.010).
Conclusion: SA exhibited analgesic effects in the formalin and writhing models, but not in the HP test. Blocking opioid receptors in the writhing test reduced the analgesic effect of SA. Exploratory behavior increased when flumazenil, naloxone, and L-NAME were injected before SA administration.

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Current Journal of Neurology

Articles in Press, Accepted Manuscript
Available Online from 23 September 2025
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