Investigation of Chronic Pain for the Development of Novel Analgesics Focusing on High Mobility Group Box-1

Neuropathic pain is an infirm type of chronic pain, which results in functional and emotional impairment. There is an urgent need for novel therapeutic approaches because there is lack of effective treatment for neuropathic pain. Posttraumatic trigeminal neuropathy (PTTN), a chronic sensory disorder following trauma, for example, during dental implant surgery or third molar removal, can cause orofacial numbness, paresthesia and pain. Unlike other painful peripheral neuropathies, the chance of developing PTTN is predictable based on preoperative assessment such as X-ray of the trigeminal nerve tract and the surgery site. High mobility group box-1 (HMGB1) acts as damage associated molecular patterns (DAMPs) and contributes to the pathogenesis of neuropathic pain including diabetic and chemotherapy-induced peripheral neuropathy. Recently, we have demonstrated that HMGB1 around injured sciatic nerves is a key molecule triggering the onset of neuropathic pain. We therefore hypothesize that inhibition of HMGB1 could prevent the onset of PTTN. In a mouse PTTN model, pretreatment with anti-HMGB1 neutralizing antibody can attenuate PTTN-induced behavioral painful responses and suppress microglial activation in spinal trigeminal nucleus caudalis. In summary, perioperative inhibition of HMGB1 activity could be used to prevent the onset of PTTN. This review summarizes recent findings regarding the role of HMGB1 in the induction of neuropathic pain and may generate new translational opportunities for pain treatment.