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Despite advances in medicine and numerous agents that counteract pain, millions of patients continue to suffer. Attention has been given to identify novel botanical interventions that produce analgesia by interacting with nociceptive-transducing channels. The aim of this review is to provide an overview of the actual knowledge of Acmella oleracea (L.) and its activities, particularly those that are anti-inflammatory, anti-oxidant, and painkiller. These activities are attributed to numerous bioactive compounds, such as phytosterols, phenolic compounds and N-alkylamides (spilanthol, responsible for many activities, primarily anesthetic). This review includes 99 eligible studies to consider the anti-inflammatory, anti-oxidant, and painkiller of Acmella. Studies reported in this review confirmed anti-inflammatory and anti-oxidant activities of Acmella, postulating that transcription factors of the nuclear factor-κB family (NF-κB …