The Science of Spicy Peppers


By Mary Carpenter

THE PAIN-relieving action of capsaicin—molecules responsible for the “heat” in chili peppers and the pungency of horseradish and wasabi—played a starring role in groundbreaking research that led to this year’s Nobel Prize in Physiology or Medicine. According to Brazilian capsaicin researchers, “We can fairly consider capsaicin as one of the most important sources of knowledge in the pain field.”

At the same time that capsaicin causes intense burning pain, it can conversely act as an analgesic (in formulations of cream and patches), countering pain that is both immediate and chronic. (“Chronic” pain by definition lasts longer than three months after the onset of injury or disease, or causes 10 or more missed work days/year.)  Most often used in treatment for nerve pain, such as that of shingles and diabetic neuropathy, capsaicin can also relieve the discomfort of rheumatoid and osteoarthritis.

(In addition, capsaicin spray used regularly over two weeks can provide long-term relief to sufferers of perennial sniffles that are caused by non-allergic hyperreactivity of the nasal passages. And topical applications can decrease sensations of itching as well as pain by causing the “defunctionalization” of relevant brain pathways.

One motivation for seeking better chronic pain treatment is the recent documentation of increased pain in dementia patients beginning years before their diagnosis. In a study of almost 10,000 British government employees, those who developed dementia reported slightly more pain as early as 16 years before that diagnosis, according to researchers at the Université de Paris. Whether chronic pain might cause or accelerate the onset of dementia, or may be simply associated with dementia because both are caused by some other factor, results suggest chronic pain might be an early indicator of dementia.

After similar findings among about 2,500 enrollees in the Framingham heart study, researchers hypothesized that “widespread pain could be a preclinical phase” of dementia — as a result of either lifestyle factors associated with chronic pain, such as decreased exercise; or higher brain levels of cortisol, caused by many stressors, that can affect cognitive decline.

The 2021 Nobel Prize winners, neuroscientist Arden Patapoutian at Scripps and physiologist David Julius at UCFS, located the gene that makes cells sensitive to heat — by way of turning on channels in peripheral sensory nerves that respond by sending pain signals to the brain. Disabling the gene in order to block sensation would be risky because sensitivity to touch helps protect against harm from burning stovetops and scalding water, and because these channels also help control body temperature.

“The sense of touch is unique in perceiving stimuli both physical (temperature, mechanical) and chemical (compounds that cause pain, itch, et cetera) in nature,” according to Patapoutian, also a Howard Hughes Medical Institute researcher. “In each modality, touch neurons distinguish noxious (painful) from innocuous stimuli, and the sensitization of touch neurons in response to injury and inflammation is the basis for many clinically relevant chronic pain states.”

Repeated exposure to “counterirritants” like topical capsaicin that act to increase nerve stimulation can make peripheral cells less sensitive. At lower doses, topical capsaicin relieves pain similarly to topical NSAIDS like Voltaren. And at the high concentrations available in prescription patches, capsaicin’s effectiveness against pain has matched that of oral drugs like gabapentin —without the side effects that include sleepiness and dizziness; or even those of OTC NSAIDS, notably stomach problems.

High-dose patches applied for 60-minute periods in a doctor’s office—often after topical numbing—can produce analgesia lasting three to six months. And liquid injectable capsaicin, under development for knee joint pain, could produce more long-lasting effects.

For self-treatment of arthritis pain, “it makes sense to give capsaicin a two-week trial to see how it works for you,” according to Clinical Medicine Professor Ted Fields at Weill Cornell Medical College and New York’s Hospital for Special Surgery. Fields suggests starting with a mid-strength (.075%) OTC patch: “if you find the burning sensation too much to cope with,” then go down to the milder strength (.025%).

Self-administering capsaicin patches, though less unpleasant after prior numbing with ice, requires care to keep treated areas away from direct heat—for example, removing the patches at least an hour before taking a hot shower or sauna as well as before vigorous exercise. And to be sure capsaicin does not come into contact with broken skin or eyes, hand-washing after use is crucial —with some people wearing gloves at night to protect their eyes.

To be worth trying, because capsaicin can be so unpleasantly irritating and because it requires such care in application, the pain being treated has to be severe enough and resistant to other remedies. For my own knees, topical Voltaren seems to have little medicinal effect but creates a soothing massage for sore knees that seems preferable to burning skin. For combating my perennial non-allergic sniffles, on the other hand, capsaicin provides immediate relief and an appealingly more natural option than everyday squirts of Flonase.

—Mary Carpenter regularly reports on topical subjects in health and medicine.

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