What is itching?

Question

What exactly at the molecular level is itching? What physiological function does itching serve, if any? I cant remember the reference but a PLCb3 null mice lost the itch phenotype, so presumably it is mediated by the Gq-PLCbeta pathway through a cell surface GPCR. Since a physical action of scratching relieves it, could it be a case of a mechanosensitive channel at work?

Answer 1

Like all tough questions, this one has no well understood answer. Itching "is one of the most poorly understood sensations."

The obvious facts: The urge to scratch part of your skin is the result of stimulus of the skin which causes some of the nerves to register an irritation (you can get an itch in internal organs too - which sounds excruciating).

Biochemically, following the effects of poison Ivy oils, the cathechols break down to orthoquinones and may stimulate local mast cells to release histimine. So in this case you can see that itching, like many irritations are linked to the immune system which is highly variable from one individual to another, as such it is still a bit of a black box.
The histamine pathway is well studied and histamine stimulates an ion channel protein in nerve cells called TRPV1, which is also known as the capsaicin receptor, which means it is also related to sensing heat. This explains why itching can be relieved (temporarily) by exposing the skin to water that is as hot as the patient can stand without burning them. This is one of the ways pain and itching are highly intertwined.

Still, not all itching is stimulated by histamine release; that isn't the whole story. Antihistamine allergy pills don't help itching. Other nerve channel proteins can be activated to stimulate itching. One example found in an itchy mutant strain of mice is TRPA1, and maybe the G protein coupled receptor, Gastrin Releasing Protein Receptor (GRPR). Its hard to imagine that there will not be more mechanisms discovered later.

Mediated both by immune systems and nerve cells, which literally have a mind of their own and whose signal processing is highly individualized and sensitive to local conditions in the body make itching a fairly mysterious phenomenon. Its also likely that itching can be entirely initiated as a mental condition (Pruritus), so it is not entirely a biochemical phenomenon, which only serves to illustrate the point I guess.