New Insight Into the Neural and Molecular Pathways for Pressure Sensation in Humans

Findings from a new study reveal a critical role for Aβ sensory neurons in pressure sensation and also suggest the involvement of an unknown molecular pathway. Recently published in Nature Communications, the study was conducted by researchers from the National Center for Complementary and Integrative Health, the National Institute of Neurological Disorders and Stroke, the University of California, San Diego, and universities in Sweden and the United Kingdom.

Pressure sensation conveys important information that the brain uses to make determinations about the body and the environment, such as the presence of tissue damage or the amount of force needed to move an object. Although the scientific understanding of touch sensation has grown significantly in recent years, less is known about the mechanism of deep tissue sensations like pressure, and particularly nonpainful pressure.

Using a blood pressure sleeve on the arms of healthy participants, researchers gradually blocked the function of sensory neurons, starting with the largest neurons. Participants lost vibration sensation (which involves medium-sized sensory neurons, also called Aβ sensory neurons) at the same time they lost the sensation of nonpainful pressure, suggesting that the Aβ sensory neurons transmitted both sensations.

The researchers then evaluated two patients without Aβ sensory neurons and seven patients with PIEZO2 deficiency syndrome, in which the PIEZO2 protein—essential for proprioception (awareness of one’s body in space), vibration sensation, and touch sensation—does not work. Patients without Aβ sensory neurons could perceive painful pressure but not nonpainful pressure, whereas patients with PIEZO2 deficiency syndrome could perceive both types of pressure, revealing that Aβ sensory neurons, but not PIEZO2, are required for nonpainful pressure sensation. These findings were confirmed by another test in which patients were asked to exert a specific amount of force on a digital scale. Patients without Aβ sensory neurons were unable to complete the task without visual feedback, whereas patients with PIEZO2 deficiency syndrome were able to complete it.

The researchers concluded that these data support a critical role of Aβ sensory neurons in nonpainful pressure sensation and reveal the existence of an unknown molecular pathway for pressure detection that doesn’t involve PIEZO2. Future research may uncover which specific subtypes of Aβ sensory neurons and which molecular pathways are involved in the perception of nonpainful pressure.