Molecular Level Answers: Do capsaicin creams really work? – by Holly Phaneuf Erskine
Even without taste buds, red pepper would still burn your mouth.
When you eat red pepper, you do not actually taste capsaicin with your taste buds. Like other oil-soluble, small molecules, it has the ability to penetrate tissues.
It slowly moves through tissues in your mouth, to trigger deeper nerves, and the classic burning sensation slowly grows.
Paradoxically, it relieves pain, but it isn’t your usual counterirritant.
Some counterirritant action may in part explain how red pepper works. However, experimenters have unearthed a far more promising mechanism.
The capsaicin in red pepper fools your brain into sensing heat when there isn’t any.
Acting just like one of your own neurotransmitters, capsaicin (cap-SAY-sin) binds to a nerve receptor called the VR1 receptor, and temporarily changes the shape of the receptor.
The VR1 receptor is ordinarily deformed by heat above around 42 oC (108 oF) and its change in shape opens the nerve cell’s gates to charged particles called ions.
Ions then flood into the nerve cell, producing a signal to a second nerve.
The signal travels from nerve to nerve to reach the brain, and pain, perceived as heat, is felt.
You think you’re are hot, but you’re not.
You even respond as if you are hot, for example, it makes you sweat.
VR1 stands for “vanilloid receptor 1”.
(Oddly enough, capsaicin looks like the vanillin in vanilla, except it has a modification that makes it more fat-soluble. Obviously it doesn’t taste like vanilla.)
Capsaicin relieves pain by depleting your nerves’ supply of substance P, the “bad pain” neurotransmitter.
Physicians classify pain as “good pain” or “bad pain”. Although you might find it hard to admit that any pain could is “good,” in fact, the short-term (acute) pain that you feel when you accidentally rest your fingers on a hot stove instructs you to jerk your hand away before it is burnt to a crisp, so it is good.
“Bad pain” is long-term (chronic) pain, and is mediated by a different neurotransmitter than the one that signals good pain.
Nerves that send good pain signals are fast, but nerves that send bad pain signals are slow, and they generate chronic, long-term pain.
The bad pain neurotransmitter is called substance P (the “P”, of course, stands for pain).
Capsaicin causes your bad pain nerves to deliver off their substance P to other pain nerves up leading to the brain in a big way.
The bad pain nerves lose so much substance P all at once that they are depleted of this molecule, and are unable to release any more.
Initially pain is felt, but after the substance P supply is dumped, the nerves are no longer able to send a pain signal to the brain, because they are all out of substance P, and don’t have time to make any more.
(Capsaicin binding to VR1 receptors triggers the release of the bad pain transmitter, substance P, initially, but substance P does not bind capsaicin’s VR1 receptors.
It binds NK1 receptors, as it travels up to your brain, and new therapeutics blocking NK1 receptors may also prove another method of relieving pain.
Incidentally, the dominant neurotransmitter signaling “good pain” is glutamate.
Whether capsaicin helps depends; are you feeling good pain or bad pain?
Bad pain nerves signal slowly, because they are poorly insulated—insulation along segments of nerves in vertebrates allows the signal to jump faster, from gap to gap in between each insulated segment.
With less of this signal-accelerating insulation, bad pain signals build slowly but take a long time to die down.
These are the same slow signaling nerves that are active in arthritis and other types of chronic, painful conditions, and capsaicin seems useful in dulling this pain.
Fast nerves are more heavily insulated, and conduct good pain, which is felt only briefly.
If you burn yourself lightly on a stove and your bad pain nerves don’t kick in to join the slow ones’ complaint, capsaicin may not help your “good” pain get any better.
A new discovery reveals your brains are spicier than you think. You don’t have capsaicin in your brain, but you have similar-looking molecules called endogenous capsaicin analogues.
You even have VR1 receptors in your brain for them to bind, but we aren’t exactly sure of all that happens when they do. It seems they are used to signal to you brain that something is wrong in your body, and they enhance your perception of pain.
For example, VR1 receptors on the heart were recently discovered, too, and the way you feel a heart attack coming on is your own versions of capsaicin bind to these receptors on your heart. They may have other physiological effects as well, like on blood pressure and respiratory airway constriction.
Evidence of Action Well-designed clinical trials have repeatedly confirmed that topical red pepper creams are indeed quite helpful in treating a number of painful conditions, including
- rheumatoid arthritis(2),
- osteoarthritis(3), as well as
- neuralgias like shingles(4), and
- diabetic neuropathy(5).
It also proved effective treating lower back pain, and in a preliminary pilot study, chronic neck pain.
It could possibly help those with fibromyalgia, but more study is required to confirm this.
A few people in these studies do not tolerate the treatment, and some have especially adverse reactions to it.
That would be me.
As I finished applying the cream to a large area of my low back, the stinging started, and it kept getting worse. It felt like someone was holding a hot iron against my back. I tried rinsing it off, but still, my skin burned fiercely for over an hour.
I find it hard to believe that this medieval torture cream actually works for other people. Perhaps it’s just such awful pain that the original pain doesn’t seem so bad?
I wish I could find an explanation of why my Substance P doesn’t get depleted and run out.
Others had to apply the cream several times a day for a week until they noticed positive results.
Red pepper apparently generates indigestion in some people, but relieves it in others.
For people who suffered ordinary chronic indigestion (without gastrointestinal reflux disease or irritable bowel syndrome), red pepper significantly reduced discomfort.
On the other hand, another study shows in people who routinely had heartburn, it made their heartburn more painful.
It really sounds like capsaicin evokes completely different and even opposite effects in different people.
I’m curious what percentage of people are like me and get no relief, just additional pain.
The Bottom Line
Red pepper contains capsaicin, which depletes nerves of a pain-signaling molecule called substance P.
Red pepper creams applied topically appear successful in relieving certain types of pain.
Red pepper creams can cause painful burning sensations if applied too liberally, or to sensitive areas like the eyes and mucous membranes.
That’s an understatement! I tried using it once more, this time applying only a tiny bit, but the searing burn started right away and persisted.
Through it’s substance P-depleting mechanism, red pepper may help certain types of indigestion, including ulcers, but make other kinds of indigestion worse, like heartburn.
More experimental data is needed to support the effectiveness of this treatment.
Humans make molecules similar to red pepper’s capsaicin. Blocking their action may lead to the invention of a new class of pain medications.