High mobility group box-1: A therapeutic target for analgesia and associated symptoms in chronic pain

The number of patients with chronic pain continues to increase against the background of an ageing society and a high incidence of various epidemics and disasters. One factor contributing to this situation is the absence of truly effective analgesics. Chronic pain is a persistent stress for the organism and can trigger a variety of neuropsychiatric symptoms. Hence, the search for useful analgesic targets is currently being intensified worldwide, and it is anticipated that the key to success may be molecules involved in emotional as well as sensory systems. High mobility group box-1 (HMGB1) has attracted attention as a therapeutic target for a variety of diseases. It is a very unique molecule having a dual role as a nuclear protein while also functioning as an inflammatory agent outside the cell. In recent years, numerous studies have shown that HMGB1 acts as a pain inducer in primary sensory nerves and the spinal dorsal horn. In addition, HMGB1 can function in the brain, and is involved in the symptoms of depression, anxiety and cognitive dysfunction that accompany chronic pain. In this review, we will summarize recent research and discuss the potential of HMGB1 as a useful drug target for chronic pain.