Decoding itch signaling mechanisms in
the skin
Both spontaneous and mechanical itch responses originate in the skin. Previous research has identified the Merkel cell-slowly adaptive Ab touch fiber complex as a key regulator of mechanical itch in normal conditions. However, in the context of aging or chronic itch associated with dry skin, the loss of Merkel cells removes the inhibition on mechanical itch, leading to the development of alloknesis (mechanical itch sensitization). Our studies have also shown that surviving Merkel cells in mice, following experimental dry skin treatment, can establish a functional connection with MrgprA3-expressing itch fibers and promote spontaneous itch. Notably, the mechanosensitive Piezo2 channels expressed by Merkel cells are essential for inhibiting mechanical itch and promoting spontaneous itch through the activation of slowly adaptive Ab fibers and C-pruriceptors, respectively. These findings have significantly contributed to our understanding of how Piezo2 channels and Merkel cells influence itch signaling in the skin. However, the mechanisms by which Merkel cells respond to tissue injury, skin inflammation, and aging, as well as the impact of these changes in Merkel cell biology on their interaction with touch and itch fibers in the skin, remain incompletely understood. Furthermore, we will investigate whether Merkel cells play a role in the development of skin inflammation, in addition to their involvement in itch signaling.
Mechanisms of Interoception
Sensory perceptions are initiated by a combination of external and internal cues, which play a crucial role in meeting our survival and psychological needs. The awareness of external stimuli, such as touch, sight, smell, sound, and taste, is known as exteroception. On the other hand, interoception refers to the perception of internal bodily states, including both unconscious processes like respiration and bowel movements, as well as conscious experiences like chest pain during a heart attack and intestinal cramps. Interoceptive signals are transmitted to the brain through two main pathways: the ascending viscerosensory pathway via the spinal cord, and the vagus sensory pathway through the nucleus tractus solitarii in the brainstem. However, our understanding of the CNS circuits responsible for processing interoceptive inputs from visceral organs is still limited. To address these gaps, we will utilize conventional genetic techniques and virally mediated intersectional genetics to identify neural circuits that are essential for both the sensory discriminative and affective components of visceral pain.