Sensory neuron PIEZO1 deletion inhibits dynamic light touch sensitivity in uninjured mice, prevents neuropathic light touch hypersensitivity, and drives compensatory changes in dorsal root ganglia.

Mechanotransduction is vital for sensing various mechanical stimuli, including blunt force and dynamic light touch. The sensation of a punctate mechanical force is very different from that of a brush swept across the skin, yet both involve mechanical stimulation of the skin and embedded sensory afferent endings. However, the sensory neuron mechanisms contributing to punctate vs light touch somatosensation, and how they might become dysregulated in nerve injury to cause pain, remain unclear. Here, we use mice with sensory neuron-specific PIEZO1 deletion to demonstrate sensory neuron PIEZO1 is required for dynamic light mechanical touch, and possibly punctate mechanical force, in healthy animals. These mice are also protected from acute and chronic tibial spared nerve injury-induced dynamic light touch hypersensitivity. However, dorsal root ganglia neurons from uninjured mice with sensory neuron PIEZO1 deletion displayed evidence of developmental compensation, including sensitized mechanically evoked inward currents. Dorsal root ganglia from these mice also exhibit transcriptional and functional compensation of other ion channels, including PIEZO2, TRPV1, and TRPV4. Thus, the behavioral phenotype of mice with sensory neuron-specific PIEZO1 knockout likely reflects these and possibly other forms of genetic compensation resulting from PIEZO1 absence throughout development, in addition to functional sensory neuron PIEZO1 deletion. Research using this transgenic mouse model must account for these caveats to facilitate accurate data interpretation. Furthermore, this article serves as a call for researchers to critically investigate possible genetic compensation in their mice. Such scrutiny is crucial to prevent replication crises and for advancement of scientific knowledge more broadly.