Title : Comprehensive evidence synthesis: Efficacy and safety of natural products in the management of chronic neuropathic pain: A systematic review and meta-analysis

Chronic neuropathic pain remains a complex clinical challenge, often inadequately managed by conventional therapeutics due to dose-limiting adverse effects and variable long-term efficacy. Consequently, natural products and isolated phytochemicals are increasingly investigated as alternative or adjunctive treatments. This systematic review and meta-analysis aim to evaluate the therapeutic efficacy, safety profiles, and underlying pharmacological mechanisms of natural products in the management of chronic neuropathic pain across preclinical and clinical studies. A comprehensive literature search will be conducted across major electronic databases (PubMed, Embase, Cochrane Library, Web of Science, and Scopus) in accordance with PRISMA guidelines. Eligible studies will include randomized controlled trials (RCTs) and well-characterized preclinical in vivo models investigating botanical extracts, isolated secondary metabolites, or nutraceuticals for neuropathic pain. Study selection, data extraction, and methodological quality assessment (using Cochrane's RoB 2 and SYRCLE's tools) will be performed independently by multiple reviewers. Extracted continuous and dichotomous data will be pooled using a random-effects model to calculate Standardized Mean Differences (SMD) and Risk Ratios (RR), with heterogeneity assessed via the I^2 statistic. The synthesis will evaluate primary endpoints including changes in mechanical allodynia, thermal hyperalgesia, and clinical pain rating scales, alongside secondary safety outcomes such as adverse event incidence and treatment withdrawal rates. Subgroup analyses will examine the comparative efficacy of specific phytochemical classes (e.g., flavonoids, terpenes, and cannabinoids) across distinct neuropathic etiologies. This review will provide a rigorous, evidence-based appraisal of natural products in pain management, identifying key therapeutic benefits, safety parameters, and methodological gaps to guide future clinical translation and integrative pain care protocols.

Dr. Emeka Ugoala is an organic chemist specializing in natural product chemistry research. He holds a PhD in Organic Chemistry from Ahmadu Bello University, Nigeria. Dr. Ugoala has worked with National Institute for Freshwater Fisheries Research on natural/micro-algae additions to fish feeds initiatives and has published extensively on natural products and food chemistry. He is the immediate past HOD of Biology and Forensic Science at the Admiralty University of Nigeria, Ibusa, Delta State.