Tmem160 contributes to the establishment of discrete nerve injury-induced pain behaviors in male mice

Chronic pain is a prevalent medical problem, and its molecular basis remains poorly understood. Here, we demonstrate the significance of the transmembrane protein (Tmem) 160 for nerve injury-induced neuropathic pain. An extensive behavioral assessment suggests a pain modality-and entity-specific phenotype in male Tmem160 global knockout (KO) mice: delayed establishment of tactile hypersensitivity and alterations in self grooming after nerve injury. In contrast, Tmem160 seems to be dispensable for other nerve injury-induced pain modalities, such as non-evoked and movement-evoked pain, and for other pain entities. Mechanistically, we show that global KO males exhibit dampened neuroimmune signaling and diminished TRPA1-mediated activity in cultured dorsal root ganglia. Neither these changes nor altered pain-related behaviors are observed in global KO female and male peripheral sensory neuron-specific KO mice. Our findings reveal Tmem160 as a sexually dimorphic factor contributing to the establishment, but not maintenance, of discrete nerve-induced pain behaviors in male mice.

Automated summary

Tmem160 plays a significant role in the establishment of nerve injury-induced pain behaviors in male mice, but is dispensable for other pain modalities and entities. The findings reveal Tmem160 as a sexually dimorphic factor in the development of specific nerve-induced pain behaviors.