Pain and Analgesia in Ethnopharmacology: Multi-target Mechanisms and Safety Boundaries

Ethnopharmacology is increasingly recognized for its potential contributions to pain management through traditional remedies and fungal and herbal extracts and metabolites derived from them. Despite centuries of use for pain relief in various cultures, the precise mechanisms underlying the analgesic actions of traditional medicines and metabolites derived from them remain only partially understood. Recent scientific inquiry has begun to delineate how these fungal and herbal extracts and metabolites derived from them interact with multiple physiological targets, contrasting with the single-target focus of many conventional drugs. However, questions persist regarding the comprehensive safety profiles, dose ranges, and long-term effects of these remedies, as well as the standardization and regulation necessary to support their wider application.Evidence from recent studies highlights the complex, multi-target nature of many botanicals and traditional analgesics, which may modulate pain through anti-inflammatory, neuro-modulatory, and immunoregulatory pathways. For example, plant extracts have been shown to impact opioid, cannabinoid, and TRP channels simultaneously, while also interfering with cytokine networks and oxidative stress responses. At the same time, reports of toxicity, herb-drug interactions, and adverse effects underscore the need for rigorous safety assessment. Despite advances in computational and systems biology, substantial gaps remain in integrating traditional knowledge, pharmacodynamic profiling, and clinical outcomes in this field.This Research Topic aims to elucidate the multi-target mechanisms by which traditional medicines and metabolites derived from them produce analgesic effects, while also critically evaluating their safety boundaries. In addition, we aim to advance the clinical evaluation and translational validation of these agents through well-designed clinical studies and real-world evidence. We seek to foster interdisciplinary contributions that bridge molecular pharmacology, clinical studies, ethnobotanical surveys, and safety science, in order to advance both our scientific understanding and practical application of these remedies in pain management.To gather further insights into the landscape and challenges of using traditional medicines and metabolites derived from them for pain relief, we welcome articles addressing, but not limited to, the following themes:• Molecular targets and pathways mediating analgesic effects of traditional remedies• Systems biology and integrated in silico and in vitro approaches to the identification of core targets and active metabolites• Toxicological evaluation and safety boundaries of traditional medicines and metabolites derived from them used in the management of pain• Herb-drug interactions and adverse event surveillance of such preparations• Standardization, quality control, and regulatory considerations of such preparations• Translational studies and clinical trials on traditional medicines and metabolites derived from them used in the management of pain• Ethnobotanical and cross-cultural perspectives on pain managementAppendix: We invite original research articles, reviews, mini-reviews, case reports, methodology papers, and perspectives.Please note:All studies must adhere to the Four Pillars of Best Practice in Ethnopharmacology and the ConPhyMP statement (Front. Pharmacol., 13:953205). Manuscripts must include detailed descriptions of biological material, extraction methods, and processing procedures; submissions lacking these details will be desk-rejected. The full best-practice guidance is available at: https://ga-online.org/best-practice.Authors are encouraged to self-assess their manuscripts using the ConPhyMP tool before submission.In silico network (‘pharmacological’) studies of complex mixtures do not result in specific pharmacologically relevant findings and will not be considered.Bibliometric studies do not contribute to pharmacological evidence mapping and will not be considered.Topic Editor Keiko Ogawa received financial support from Tsumura co.. The other Topic Editors declare no competing interests with regard to the Research Topic subject. Topic editors: Keiko Ochiai Ogawa, Dongwoo Nam, Mitsuru Doi Source: https://www.frontiersin.org/research-topics/79668/pain-and-analgesia-in-ethnopharmacology-multi-target-mechanisms-and-safety-boundaries