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Chronic sciatica (CS) is a common condition of disability and pain. Lawsonia inermis L. (henna) is a medicinal plant that is commonly recommended in traditional Persian medicine textbooks for pain relief in patients with sciatica, particularly in the form of oil. This research was designed to investigate the efficacy of a topical formulation from henna on pain intensity in patients with CS. In a randomized, double-blind clinical study, 81 patients were randomly allocated to three groups to receive the topical henna formulation (aqueous extract of henna in sesame oil), sesame oil, or placebo, three times daily, for four weeks. The patients were assessed by visual analog scale (VAS), 36-item short form health survey (SF-36), and Oswestry disability index (ODI). There was a significant decrease in mean VAS in henna oil compared to sesame oil (p = 0.004) and placebo (p = 0.004). Significant improvements in total SF-36 scores were observed in henna oil and sesame oil compared to placebo (p = 0.011 and p = 0.025, respectively). Furthermore, ODI significantly decreased in henna oil compared to sesame oil (p < 0.001) and placebo (p = 0.005). Henna oil seems to be an effective treatment to reduce pain intensity in patients with CS. Moreover, it improves quality of life and functional ability. Further randomized controlled trials with longer intervention periods are recommended to confirm this efficacy. [Display omitted] • Henna has been frequently cited for pain relief of sciatica in Persian medicine. • The topical henna oil reduced pain intensity in patients with chronic sciatica. • Henna oil improved quality of life and functional ability in chronic sciatica. [ABSTRACT FROM AUTHOR]