Chilli peppers and capsaicin
There are two big ironies in my journey healing migraine. One irony is that I grew up in a part of the world rich in copper, home to some of the world’s largest copper mines – but copper deficiency was playing a big role in my migraine pattern. Another irony is that I grew up a few miles from the famous Hatch Chile fields of southwestern New Mexico. Yet spicy food has been the biggest migraine trigger for me historically, enough so that I still choose to avoid spicy food during my moon-time to avoid brain fog even now that my chronic migraine pattern is resolved.
It took me years to solve the mystery of these two issues: copper and chili. Today I want to focus on chili and the main compound that gives it its spicy (and headachey) kick – capsaicin.
Capsaicin and TRP channels
Capsaicin is the molecule in pungent, spicy foods that gives it the burning sensation of hot on the tongue. It’s quite incredible that the body is able to sense heat and cold even in the absence of actual heat and cold, through molecules like capsaicin or (for cold) menthol that act on cells via something called TRP channels. TRP channels are ion channels located on the plasma membrane of cells that help the body to sense and respond to it’s environment.
There is an underlying system, the equivalent of a chemical radar system that allows us to navigate the world, warning us of problems & invaders, as well as reminding us of friends and the familiar. This is achieved through the same super family of receptors called TRPs. TRPs are your chemical radar system used to detect friends and foes. The sensations under their control are important to daily function. They dictate quality of life and allow us to navigate through our environment. Sensations include: pain, heat, coolness, taste, nausea, cough and pheromones. They also mediate local responses like blood flow, cough, histamine & hormone release. (Source)
Capsaicin, as it turns out, is such a strong agonist (amplifier) of TRP channels that it is frequently used in science to study these channels, although there are multiple TRP channels, with capsaicin acting primarily on the vanilloid receptor-1 (VR-1) of the TRP channel (also known as TRPV1).
(As an aside: it’s interesting to note that TRPV1 channels are activated by pH changes. That lends an additional layer of insight to my theories around why acidic foods trigger migraine.)
TRPV1 channels, CGRP, and migraine
TRPV1 channels have been shown to be involved in the pathophysiology of migraine. The anti-migraine drug sumatriptan was recently shown to block trigeminal TRPV1 channels. The activation of TRPV1 causes a release of CGRP from the trigeminal nerves, followed by inflammation within the meninges (the tissue surrounding the brain).
You may have heard about the new generation of calcitonin gene-related peptide(CGRP) inhibiting drugs out there (shots like Aimovig). CGRP is a neuropeptide in the brain that causes blood vessel dilation and migraine at elevated levels. The new CGRP receptor antagonist drugs aim to blunt the receptivity of the neurons to this peptide. Capsaicin, on the other hand, increases sensitivity to CGRP via activation of the TRPV1 channels – ie, it is a TRPV1 and CGRP agonist, not antagonist. Researchers who injected capsaicin into the carotid artery caused a significant increase in jugular CGRP levels.
TRPV1, capsaicin, and osmotic pressure
Migraineurs will be familiar with the sensation of brain swelling during migraine. This swelling occurs from changes in osmotic pressure in the brain, which in turn causes impingemenet on the innervated tissues of the meninges surrounding the brain. So it’s interesting that TRPV1 channels are also involved in regulation of osmotic pressure.
TRPV1 sense osmotic changes, specifically hypertonicity. A 2010 paper shows that there is a TRPV1 in the brain that does not react to heat or capsaicin, but does respond to osmotic stress. TRPV1 sense cell shrinkage and signals the hypothalamus of the brain to release a hormone called vasopressin (also called ADH). This hormone causes more water to be retained and more salt to be excreted. This lowers the salt concentration outside the cells and the cell shrinkage can be corrected. (Source)
So imagine you’re experiencing a lot of stress, not hydrating and not eating well – sound familiar? Your muscles (especially neck muscles) get tight, and this hypertonicity triggers the TRPV1 channels to send a signal to adjust osmotic pressure, leading to salt excretion. This may explain why stress reduction, hydration, massage, and eating salt are all generally very supportive of those with migraine.
Incidentally, I’ve observed in my coaching practice that quite a few migraineurs have issues with osmotic pressure in the ear – ache in the ear, tinnitus, and even hearing loss in the ear. The TRPV1 channels are likely involved here as well.
A 2013 study indicates that TRPV1 is important for the uptake of the drugs into the hair cells. . . An older study shows that even without drugs to be taken up, increased TRPV1 expression is the cause of acoustic injury tinnitus (ringing) and hearing loss. Another paper showed that capsaicin itself blocks the action potential in the outer hair cells and dampens the cochlear amplification system. (Source)
This is really interesting, because it implies that for those with migraine, over-activation of TRPV1 channels may be what is leading to a buildup of pharmaceutical and other toxins in the ears – and it explains why detoxification and mineral balancing reduces or resolves the ear pressure. It certainly did mine. I’m grateful to mineral balancing for giving me back normal pressure in my ears.
Herpes viruses and TRPV1 channels
It’s common for migraineurs to have herpes virus infections. In a previous post on Herpes and Migraine, I shared research showing that capsaicin has been found to trigger herpes viruses. It does so in part by – you guessed it – activating TRP channels.
“Herpes simplex virus type 1 (HSV-1) produces a life-long latent infection in neurons of the peripheral nervous system, primarily in the trigeminal and dorsal root ganglia. Neurons of these ganglia express high levels of the capsaicin receptor, also known as the vanilloid receptor-1 (VR-1). VR-1 is a non-selective ion channel, found on sensory neurons, that primarily fluxes Ca(2+) ions in response to various stimuli, including physiologically acidic conditions, heat greater than 45 degrees C and noxious compounds such as capsaicin. Using an in vitro neuronal model to study HSV-1 latency and reactivation, we found that agonists of the VR-1 channel – capsaicin and heat – resulted in reactivation of latent HSV-1. . . . Taken together, these results suggest that activation of the VR-1 channel, often associated with increases in intracellular calcium, results in HSV-1 reactivation in sensory neurons.” (Source)
So, BOTH herpes and capsaicin increase CGRP levels. Oh yeah, and HEAT. So eating some spicy salsa, then taking a sauna or hot bath, would be a recipe for disaster if you have herpes infecting your trigeminal nerve.
Capsaicin can inhibit liver detoxification
As if all of this weren’t enough evidence for how and why capsaicin in chilli triggers migraine, there’s more. Turns out that capsaicin is implicated in slowing down a phase-2 liver detoxification pathway called glucuronidation.
It’s REALLY valuable to have that pathway optimized, since glucuronidation is responsible for making hormones and toxins water-soluble via bile flow. Migraineurs, with their chemical sensitivity, hormone imbalances, liver stagnation, and tendency towards gallbladder issues will want to do everything in their power to support (not inhibit) this pathway. That’s why avoiding capsaicin is important.
Capsicum annum (chili pepper) has been shown to increase levels of beta-glucuronidase in rats which will reverse glucuronidation.
Piperine from black pepper has been shown to inhibit glucuronidation and is used in conjunction with curcumin to keep it from being metabolized via glucuronidation. (Source)
I cover my favorite ways to support glucuronidation using Mother Nature’s healing plants in my online course, Holistic Migraine Relief 101.
Topical capsaicin for pain relief
If TRPV1 is stimulated long enough, the ion channel becomes desensitized. This explains its analgesic effect. People that eat hot chilli food without issues have desensitized their TRPV1 receptors. In essence the channels become unresponsive and less effective.
This explains why a topical application of cayenne to the nasal passages can prevent migraine by way of numbing the trigeminal nerve portion in the nose. However it is not always powerful enough to counteract the other areas of nerve inflammation deeper in the head that cannot be reached by topical application.
Summary
Capsaicin is a powerful compound, able to act as a pain-relieving analgesic applied topically, but also a potent migraine trigger taken internally. It acts via TRPV1 channels, the same channels that activate CGRP and lead to inflammation of the trigeminal nerve. By activating TRPV1 channels capsaicin is also implicated in herpes flares and pressure changes in the ear. Capsaicin also inhibits a pathway in the liver called glucuronidation, which is involved in neutralization of toxins and hormones via bile flow.
Knowing this, it's no surprise that capsaicin in spicy food is such a potent migraine trigger - by far one of the most potent of all. So, despite the other health benefits of chilli peppers, it's best for migraineurs to stay away from spicy food while they work on rebalancing their minerals.
Stay tuned for next week's blog post on TRPV1 agonists and antagonists.
