Pain is a physiological response to identify potentially harmful conditions and prevent tissue damage. The perception of pain is a complex signalling pathway caused by the interaction between peripheral nociceptors and primary efferent neurons, and the higher-order processing centre in the brain. The transmission of noxious stimuli from receptors to the central nervous system occurs in three major stages: transduction, transmission, and modulation. As a natural physiological response to tissue damage and dangerous signals, inflammation plays a pivotal role in sensitizing peripheral pain, via mediating the generation of pro-inflammatory cytokines, chemokines, prostaglandins, neuropeptides, and growth factors.

Pain, especially chronic pain, is a serious health concern affecting the quality of life of over one-third of the population all over the world, costing billions of dollars per year. Pain often occurs concurrently with hypertension and other cardiovascular risk factors. Treating patients with arthritis and other painful conditions who have hypertension or cardiovascular disease can be a challenge because of potential risks associated with the agents commonly used to treat pain and inflammation, and vice versa. Opioid drugs like morphine and oxycodone are the most efficacious and widely used management of severe and chronic pain. However, the side effects associated with the long-term treatment of opioid drugs, such as constipation, respiratory depression, tolerance, and addiction, not only limit their use for chronic pain but also increase the risk of opioid abuse. Furthermore, opioid drugs show less analgesic activity for some pain types, including neuropathic or musculoskeletal pain. Therefore, discovering complementary or alternative drugs for pain treatment will play a critical role in the discovery of safer pain drugs. Natural products or herbal medicines have shown health benefits as dietary supplements and drugs for the prevention and treatment of various diseases, including pain, hypertension, and cardiovascular disease. Terpenes, alkaloids, flavonoids, and cannabinoids have demonstrated themselves as strong candidates for the development of new drugs for chronic pain treatment. One potential mechanism is the modulation by natural products of the release of inflammatory mediators, such as cytokines, chemokines, and neurotransmitters. In addition to drug treatment, acupuncture has been promoted as a complementary therapy for chronic pain such as back and neck pain, osteoarthritis/knee pain, and headache.

This Special Issue aims to highlight the latest research that will help in discovering novel therapies for pain using natural products, traditional herbal medicine, complementary therapies such as acupuncture, or a combination of these. In addition, we aim to determine the mechanisms by which natural products or herbal medicine can relieve pain. Therefore, we sincerely invite researchers to contribute preclinical and clinical research as well as review articles focusing on pain and pain management, which could provide a better understanding of pain relief therapies and related drug discovery.

Potential topics include but are not limited to the following:

• Investigation of analgesic activity of natural products on animal models
• Discovery of natural products for pain management
• Development of novel pain management using natural products
• Impact of natural productions on opioid-induced analgesic activity and side effects
• Molecular and cellular mechanisms by which natural products regulate pain and inflammation
• Clinical trials on natural products for pain management
• Clinical trials on acupuncture and herbal medicine for pain management