A nociceptor is a sensory receptor that responds to potentially damaging stimuli by sending nerve signals to the spinal cord and brain. This process, called nociception, usually causes the perception of pain.

When we feel an itch, we scratch it without thinking twice. But what causes itch in the first place? Why do we even have it? Our innate reaction to everyday itch is to scratch it, but in some skin diseases that cause chronic itch, scratching exacerbates the problem.

Dr. Robert LaMotte, Professor of Anesthesiology and of Neurobiology at the Yale School of Medicine, conducts experiments on the perception and biological mechanisms of itch, using psychophysical and electrophysiological methods to measure the sensations of itch and responses of itch mediating sensory neurons.

The Biology Behind Itch

“Nociceptive” sensory neurons with small diameter nerve fibers are responsive to nox¬ious stimuli. A subset of nociceptive nerve fibers that terminate in the skin, respond to one or more chemicals that make us itch.

These neurons are termed “pruriceptive” (from the latin word, prurere, “to itch”) whereas nociceptive neurons that do not respond to itchy chemicals are called “nociceptive specific.”

Both types of neurons project to pathways in the central nervous system. So how does the brain decode itch from pain?

LaMotte explained that the current thinking in the field is that activity in nociceptive specific neurons is interpreted by the brain as “pain,” whereas activity that occurs solely in the pruriceptive population is felt as “itch.”


More than a decade ago, scientists in Germany found that histamine, a substance usually released during allergic reactions and causes itch, triggered activity in a specific type of nerve fiber terminating in the skin in humans.

Most neurons that respond to histamine also respond to other types of stimuli, such as noxious heat, mechanical stimulation, or to capsaicin, which produces burning and stinging pain when injected into the skin.


Since the discovery of histamine’s connection to itch, research has elucidated a wide range of nociceptors, some nociceptive specific and others pruriceptive.

Certain nociceptors respond to capsaicin and histamine; others respond to noxious heat and capsaicin but not histamine, and still others respond irregularly to mechanical stimuli, heat and histamine and to other itchy chemicals such as certain proteases.

For example, one type of protease is contained in the hairs (spicules) of a tropical legume called cowhage (Mucuna pruriens). When these spicules fall off the pods of the plant their tips can stick into the outer layer of skin causing a prickly itch but without the release or presence of histamine.

Because most types of clinically important itch are not relieved by anti-histamines, cowhage spicules have been useful in experiments that have identified a mechanosensitive, histamine independent pruriceptive neuronal pathway.

Activity in these mechanosensitive neurons may explain why when patients with atopic eczema, a skin disease with chronic itching, put on wool sweaters, the mechanical rubbing of the wool against the skin causes itching.

“We are trying to figure out how all the signals get sorted out in the central nervous system,” says LaMotte. “The goal is to identify the sensory neurons and pathways that mediate pain and itch, as they are very diverse and differ in many properties.”

Currently, there is no proven hypothesis on the functional basis of scratching the kind of transient itch we experience every day. One proposed idea suggests that since our skin serves a function of keeping fluids in and external irritants out, itchiness directs our attention to that area of our body so we can scratch and eliminate an irritant or parasite.

“Parasites, though, can enter our body very quickly,” points out LaMotte, “So the chances of eliminating them by scratching are not very plausible.”

LaMotte proposes another possibility. Nerve endings are activated when our skin barrier is breached and a chemical irritant (for example from microorganisms living on the skin, activate pruriceptive nerve endings thereby resulting in itch and site-directed scratching.

The scratching produces a minor “injury” that may trigger an inflammatory response that hastens the repair of the breach in the skin barrier.