Effect of subdiaphragmatic vagotomy on acute inflammatory pain

Abstract

Subdiaphragmatic vagotomy (SDV) produces analgesic effect in various pain conditions including not only visceral pain but also somatic pain. I aimed to determine how SDV induces analgesic effect in somatic pain condition by using formalin-induced acute inflammatory pain model. I analyzed c-Fos expression in the whole brain and identified specific brain region mediating SDV-induced analgesic effect on acute inflammatory pain. I found that c-Fos expression was specifically increased in the anterior insular cortex (aIC) among subregions of the insular cortex in acute inflammatory pain, which was reversed by SDV. These results were not mimicked in female mice, indicating sexual-dimorphism in SDV-induced analgesia. SDV decreased c-Fos expressions more preferentially in glutamatergic neurons rather than GABAergic neurons in the aIC, and pharmacological activation of glutamatergic neurons with NMDA (1 μg/μL) in the aIC inhibited SDV-induced analgesic effect. Taken together, this study suggests that the decrease in the neuronal activity of glutamatergic neurons in the aIC mediates SDV-induced analgesic effect, potentially serving as an important therapeutic target to treat inflammatory pain.