Antibody drugs have been widely applied to various diseases such as cancer and rheumatoid arthritis. Recently, antibody drugs against amyloid-β have attracted attention as a therapeutic agent for Alzheimer's disease, and are also expected to be applied to central nervous system diseases. On the other hand, delivery of antibody drugs to the central nervous system is not easy due to the existence of the blood-brain barrier and other barriers. Intranasal administration is a method of direct drug delivery from the nasal cavity to the brain without blood flow, and drugs are transported into the brain through the olfactory and trigeminal nerves, or the intercellular spaces and parenchyma of the olfactory epithelium. This method is considered to be particularly suitable for the administration of macromolecular compounds, and several biopharmaceuticals have already been marketed as nasal drop formulations.

We have focused on the role of high mobility group box-1 (HMGB1), one of the damage-associated molecular patterns, and the proinflammatory cytokine interleukin-6 (IL-6) in chronic pain and investigated their potential as novel drug targets. In this symposium, we will present the effects of intranasal administration of HMGB1 and IL-6 antibody on nociceptive hypersensitivity and emotional and cognitive dysfunction associated with long lasting pain in chronic pain models.