TRPM8: a counter-sensory pathway in the throat
TRPM8, or Transient Receptor Potential Melastatin 8, is an ion channel involved in the detection of cool temperatures and cooling compounds. It is expressed by subsets of cold-sensitive sensory afferents, including fibers involved in throat sensory signaling.
In refractory chronic cough (RCC), hypersensitive cough polymodal fibers can transmit exaggerated cough-triggering inputs from the throat to the brainstem “cough center,” contributing to throat irritation, urge to cough, and repeated coughing.
Axalbion’s scientific hypothesis is that AX-8 activates TRPM8-expressing cold fibers in the throat, thereby generating a counter-sensory signal that helps inhibit cough-triggering inputs from polymodal cough fibers within the cough center. Through this central gating mechanism, TRPM8 activation may modulate the abnormal sensory signaling and hypersensitive cough reflex.
This concept is supported by analogous sensory-gating biology described in the skin, where activation of TRPM8-expressing cold fibers by cold or cooling compounds can inhibit pain- and itch-related sensory inputs in the spinal cord.
