A tale of two neurons in the upper airways: pain versus itch.

Pain and itch sensations are induced by depolarization of distinct populations of unmyelinated type C, and possibly other, neurons. Both sets of neurons and sensations serve critical protective mechanisms that maintain the integrity and patency of the upper airways. When noxious or pruritic stimuli are applied on the afferent nerve ending, pain and itch are appreciated at the thalamic and parietal cortex. In the mucosa, this neuronal depolarization spreads via the peripheral efferent axon response mechanism. Neuropeptides such as substance P and calcitonin gene-related peptide are released from neurosecretory varicosities on the nociceptive C fibers. The exact functions of axon responses differ between humans and rodents, and in health and disease. Separate itch- and pain-specific peripheral type C fibers, secondary relay interneurons in the spinal cord dorsal horn, anatomical locations in the lateral spinothalamic tract, and thalamic nuclei demonstrate that all nociceptive nerves are not the same. Other types of irritant-sensitive trigeminal neurons might be discovered that could mediate other unique sensations, specific axon responses, or central nervous system functions.