After reading this story I started wondering about the main active component of chillis, capsaicin (8-Methyl-N-vanillyl-trans-6-nonenamide).
As anyone who has chopped chillis before can testify, capsaican is severe irritant to humans and other mammals and capable of causing severe pain. Interestingly birds seem unaffected by capsaicin and feed on chillis - this is a nice piece of evolution as chilli seeds don’t germinate if they’ve passed through a mammalian digestive tract but do if it’s avian.
In vivo, capsaicin binds to vanilloid receptor subtype1 (TVPR1), opening it and allows ions to flow. TVPR1 is involved in pain transmission and is also opened other stimuli such as heat or acids - hence capsaicin causes that lovely burning sensation.
Whilist writing this I stumbled across and this story. Basically inject capsaicin and an analgesic and the former will allow the latter to enter only neurons that provide pain response leaving others unaffected thus reducing numbness etc.
One small stumbling block though…
Dr Joan Hester, the president of the British Pain Society, said that while capsaicin had been used for many years to reduce skin sensitivity linked to chronic pain, it caused an unpleasant burning sensation that was too much for some patients.
This might be even more of a problem if the chemical was injected below the skin, she said.
“The technique has not yet been tried on humans, and it is hard to see how capsaicin could be used in this situation.”
I’ve add some more info on this once I’ve read the paper, apparently it’s in Nature but I can’t find it yet.
Update: the paper has been published and can be found here.
In response to PJ’s comment, they do appear to have used capsaicin and the analgesic (QX-314) alone as a controls. There is an increase in pain threshold when QX-314 injection is followed by capsaicin injection in both tests, heat and mechanical. If anyone with more knowledge of anaesthesia would like to follow up I’d be interested.
Interesting, a better description of the study is here
but I can’t find it in Nature yet.
I hope they properly differentiated the irritant and (alleged) counterirritant properties of capsaicin by using a capsaicin only control (can’t tell from that article) since you might expect that injecting capsaicin around a nerve (!) might produce such a burning that heat perception was disrupted.
You’d have thought a different vanilloid ligand might be a better approach, maybe a salicylate.
Edited by badchemist to make link shorter.
Speaking as a bioscientist who works a bit on ion channels and has even dabbled in this specific area, it is a surprise that QX314 would pass through the ion channel pore into the cell. These channels are what we call “cation non-selective”, but that typically means they let through alkali and alkaline earth metal cations - Na+, K+, Ca2+. QX314 is a substantially bigger molecule - it is lidocaine with an extra ethyl group on the terminal substituted nitrogen, so that it is now a quaternary amine and therefore has to be a cation. Thus one might expect it to be “size excluded” from going through unless the channel pore is quite “big” in molecular terms. This is something that has not previously been reported for this class of channels, although there are some vague precedents for other types.
BTW, as you probably know most local anaesthetics are ionizable weak bases - like QX314’s “parent” lidocaine which is a tertiary amine - and get into cells by diffusion across the membrane in the uncharged form, following which they ionize and block the channel from the inside as the charged species).
I suppose the implication is that the QX314 molecule is adopting a sort of linear-ish form and “wiggling” its way through the open channel. Anyway, a very interesting paper, but I wil be watching to see how quickly it gets confirmed by other labs.