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.

Episodic pain in Fabry disease is mediated by a heat shock protein-TRPA1 axis.

Two-thirds of patients with Fabry disease suffer debilitating pain attacks triggered by exercise, fever, and exposure to environmental heat. These patients face an even greater risk of heat-related episodic pain in the face of global climate change. Almost nothing is known about the biological mechanisms underlying heat-induced pain crises in Fabry disease, and there is no preclinical model available to study Fabry crises.

Increased keratinocyte activity and PIEZO1 signaling contribute to paclitaxel-induced mechanical hypersensitivity.

Recent work demonstrates that epidermal keratinocytes are critical for normal touch sensation. However, it is unknown whether keratinocytes contribute to touch-evoked pain and hypersensitivity after tissue injury. Here, we used a mouse model of paclitaxel treatment to determine the extent to which keratinocyte activity contributes to the severe neuropathic pain that accompanies chemotherapy.

High-speed imaging of evoked rodent mechanical behaviors yields variable results that are not predictive of inflammatory injury.

Few analgesics identified using preclinical models have successfully translated to clinical use. These translational limitations may be due to the unidimensional nature of behavioral response measures used to assess rodent nociception. Advances in high-speed videography for pain behavior allow for objective quantification of nuanced aspects of evoked paw withdrawal responses.

Keratinocyte Piezo1 drives paclitaxel-induced mechanical hypersensitivity.

Recent work demonstrates that epidermal keratinocytes are critical for normal touch sensation. However, it is unknown if keratinocytes contribute to touch evoked pain and hypersensitivity following tissue injury. Here, we used inhibitory optogenetic and chemogenetic techniques to determine the extent to which keratinocyte activity contributes to the severe neuropathic pain that accompanies chemotherapeutic treatment.