Background: Orofacial pain is a form of inflammatory pain usually treated with corticosteroids, which have many side effects. 
Objective: The aim of this study was to investigate the clinical and histological profile of antinociceptive effects of hydroalcoholic extract of caper (Capparis spinosa) for the first time in the orofacial region.
Methods: This experimental study was carried out at Babol University of Medical Sciences in 2018. Thirty-six male Wistar mice were divided into 6 groups: The first group received saline, the second group received dexamethazone, and four groups received different doses (10, 20, 50, 100 mg/kg) of caper extract. In the formalin test, 1% formalin solution was injected into the right submucosal layer of the lip and lateral area of the nose. Pain intensities were recorded at 5-min blocks for 60 min after injection. Dose effect of caper on pain was recorded. The mice were euthanized and the oral area was biopsied and stained with Hematoxylin-eosin, Toluidine blue, and Congo red. Data were analyzed using repeated measures ANOVA and t-test by IBM-SPSS version 20.
Results: Caper produced antinociceptive effects in comparison with saline groups (p<0.001). Dose effect on pain was significant (p<0.001). The highest antinociceptive effect was observed in the caper group receiving 100 mg/kg of agent 15-20 minutes after injection. The highest pain level was observed in the group that received 20 mg/kg of caper (p<0.001). Dexamethazone antinociceptive effect was greater than that of the saline and the dose of 20 mg/kg of caper (p<0.001). Antinociceptive effects in two groups (100 mg caper and dexamethazone) were equal (p>0.999). Histopathologic examination revealed the highest thickness of epithelium, fibrous, and muscular tissue density and the lowest inflammatory infiltration at the dose of 100 mg/kg of caper.
Conclusion: The results of the present study suggest that hydroalcoholic extract of caper possesses antinociceptive activity in a dose-dependent manner and caper-induced antinociception might be mediated, at least in part, by anti-inflammatory effects.
Keywords: Caper, Orofacial pain, Formalin test, Histopathology, Antinociception


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