LAUSR

Significance Persistent pain hypersensitivity associated with inflammation, surgery, trauma, and nerve injury interferes with physical and mental activities and impairs quality of life. Herein, we showed that the chemical ablation of isolectin B4-binding (IB4+) afferents suppressed inflammation- and tissue injury–induced mechanical pain hypersensitivity. We identified Tmem45b as a somatosensory-specific molecule that was down-regulated in IB4+-ablated dorsal root ganglia and confirmed its predominant expression in IB4+ primary afferent neurons. Tmem45b-knockout mice showed normal responses to noxious mechanical and noxious thermal stimuli but did not exhibit mechanical pain hypersensitivity in the setting of inflammation and tissue injury. Our findings provide insights into the mechanisms and therapeutic targets for mechanical pain hypersensitivity.