Heat, spice, itching and the "hot" receptor

Here in Massachusetts today, am watching a "bombogenesis" snow episode from the comfort of my apartment, a mug of hot black tea by my computer (BTW, it's Hot Tea Month!). One of the consequences of the cold is dry skin. My dry skin itches like crazy, and after I scratch it feels boiling hot. So I thought I needed to know more about what an itch is and why I get that hot sensation after scratching enough that the itch goes away.*

Turns out that there are (at least) four types of itch. The one I'm experiencing right now is pruritogenic—you can find out about the other kinds at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696473/. 

The diagram below, from that article, shows the mechanism for pruritogenic itch. What fascinated me was that our old friend TRPV1, the "hot" receptor that responds to chili peppers for example, lies right smack-dab in the middle of the pathway that itch sensations follow from skin nerve ending to brain!

Caption from the article: Molecular anatomy of itch. Channels and receptors on the surface of keratinocytes and nerve fibers respond to various mediators. Several examples are provided. The mechanisms by which keratinocytes and neurons communicate with each other are under investigation. DRG, dorsal root ganglia; IL-31, dorsal root ganglia; GPCR, G-protein coupled receptor; TRP, transient receptor potential [TRPV1]. 

The theory about itch is that once you apply pain through scratching, the nerves that communicate pain somehow turn off the signal to the brain coming from the nerves that communicate itch, so you are left with pain (the milder the better of course). 

I think that the reason I feel heat as well as pain after scratching an itch is that the TRPV1 receptors that are activated by the itch either stay activated and now send a "hot" message, or that the itch TRPV1 receptors also turn on the heat TRPV1 receptors, which in my case happen to be very sensitive.

Why very sensitive? I am unfortunate enough to be homozygous for a single nucleotide polymorphisms in my TRPV1 genes that increase the function of TRPV1. It's called rs161364, and I am the relatively rare person who carries two copies of this gain-of-function mutation.** The result is that I am highly sensitive to the burn of pepper, chilis, and alcohol, and apparently also the burn of an itch. (Many of the compounds in black tea also activate TRPV1, though not to the extent of causing pain).

If you are curious about your status and have done 23andme, you can look up the snp rs161364   in your raw data. A "C" gives you normal function of TRPV1, and a "T" gives you a gain-of-function. I happen to have two "T"'s. If you have one "T" your sensitivity is intermediate.

Incidentally, J. Craig Venter, whose whole genome was the first human genome to be completed, also has two copies of "T."

* Of course I don't recommend scratching—that leads to real skin problems. Better to moisturize your skin.

** 10% of Europeans like me, 5% of East Asians, and 0% of Subsaharan Africans carry 2 "T"'s.





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