Current research progress in identifying the mechanism of berberine in pain regulation

Pain is accompanied by high morbidity and imposes a substantial economic burden on individuals and society. Unfortunately, few effective therapeutic methods are available for pain relief. Berberine is a natural product that has attracted widespread attention in recent years. Studies have shown that berberine has various pharmacological effects, such as analgesic, anti-inflammatory, anti-bacterial, anti-oxidative stress, anti-thrombotic, anti-tumor, and hypoglycemic activity. According to the literature, berberine exerts its pain-relieving activity by downregulation of transient receptor potential vanilloid (TRPV)-1; suppression of toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-B (NF-κB); and modulation of μ opioid receptors. Moreover, berberine could regulate the dopamine and N-methyl-D-aspartic acid (NMDA) systems and induce the expression of Nrf2 to promote analgesia. The present literature review discusses the analgesic effects of berberine in inflammatory pain, neuropathic pain, cancer pain, chemotherapy pain, and morphine tolerance, and discusses the possible mechanism of berberine in pain regulation.