OBJECTIVE: The treatment of neuropathic pain is crucial, as it not only alleviates physical discomfort but also reduces anxiety associated with pain, ultimately enhancing the quality of life for affected individuals. This study investigates the protective effects of hydro-alcoholic extracts from Eryngium billardieri (Er) and Urtica dioica (Ur) on neuropathic pain and anxiety responses in an animal model. METHODS: 40 male Wistar rats were used to investigate neuropathy induced by the chronic constriction injury (CCI) model. Animals were divided into five experimental groups (N=8): [sham], [CCI], [CCI+Er], [CCI+Ur], and [CCI+Imipramine]. Er and Ur were administered orally for 30 days, starting on the day of surgery. Behavioral tests, including acetone for cold allodynia, the elevated plus maze for anxiety-like behaviors, and the open field for innate anxiety, were conducted on day -1 (before CCI) and on days 2, 4, 6, 14, 21, and 30. Data were analyzed by one-way analysis of variance test, and P<
0.05 was considered significant. RESULTS: Neuropathic surgery resulted in cold allodynia and anxiety-like behaviors throughout the experiment as compared to the sham. Er extract significantly decreased both cold allodynia and anxiety-like behaviors in the CCI group. However, Ur extract only significantly reduced cold allodynia (and not anxiety-like behaviors). Additionally, there was no difference between the analgesic effects of Er and Ur extracts. CONCLUSIONS: These findings support the use of Er as a potential comprehensive treatment for neuropathic pain and anxiety symptoms. Future research should focus on exploring the specific mechanisms behind these effects and the potential for synergistic treatments to improve outcomes for individuals suffering from neuropathy.