Columbus, Mutant Mice and Pepper Therapy

Science and Technology

May 11, 2000 at 2:06 pm

Peppers. Red Chile peppers; bell peppers; banana and Hungarian cherry peppers; Jalapeño peppers; Szechuan peppers; cayenne, Habanero and Tabasco peppers.

Just thinking about them makes your tongue tingle.

But researchers believe that, in peppers, they've uncovered some of the many mysteries of pain reception and its management. The work might lead to completely novel ways to treat chronic pain.

The pepper is yet another of the numerous tasty wonders brought back from the New World to the previously boring Old World by Christopher Columbus. There are more than 200 varieties, used widely in African, Indian, Chinese, Thai, Mexican and South American cuisine. They range in size from 12 inches to just a half-inch. There are green, yellow and red; some are long and thin, others are round.

But they all make your mouth burn to varying degrees.

They all turn your face various shades of red. And they all have you reaching for a glass of water.

The culprit responsible for this universal response is a compound called capsaicin. Found mainly in the seeds and membranes of the pepper, capsaicin results in that familiar burn you experience when eating spicy food.

In a recent issue of the scientific journal Science, researchers reported successfully breeding mutant mice that didn't respond to capsaicin. The mice behaved normally in most respects and looked just like normal mice but showed less sensitivity to pain, high temperatures and normally noxious stimuli. Although this doesn't sound very important, these results might revolutionize pain medication.

The brain receives sensory information — taste, touch, temperature and pain — from peripheral nerves present in all parts of the body. A nerve transmits sensory information from the periphery in the form of an electrical impulse that travels first to the spinal cord and then on to the brain, where it can be interpreted.

On the surface of nerve cells are specific receptors for substances that initiate this impulse by moving charged ions from one location to another. Cells are specific, so some respond to pressure and some to heat. Others are part of a specialized sensory system such as vision or hearing. The brain has distinct areas that receive sensory information, connected to higher thought centers that interpret them and motor centers that can respond appropriately.

OK, I know it's tricky.

Try this fun experiment: Go to the store and buy a chicken chimichanga burrito for 69 cents, remove from wrapper and microwave for two minutes on high power, cover chimichanga with excessive amount of Tabasco sauce and eat chimichanga.

How does that feel? It's hurting? It burns? Holy crap, make the pain stop? This is the normal response.

The nerves in your tongue have receptors that are specific for the capsaicin in the Tabasco sauce you poured all over your Chimichanga. The capsaicin molecules bond to the receptor for which they were a perfect fit, changing the structure of the receptor and allowing charged ions to move from one location in the nerve to another. In this way, an electrical nerve impulse was initiated that quickly traveled via the spinal cord to the brain. The brain subsequently interpreted the capsaicin as heat, pain and a sudden desperate need for water.

Unless you're a mutant mouse.

Remember those little guys? Due to a genetic mutation, they have no capsaicin receptors at all. The researchers gave them drinking water laced with capsaicin and they drank freely with no adverse effects. Normal mice "took one sip of the capsaicin-containing water, rubbed their snouts vigorously and avoided further consumption." In normal mice, subcutaneous injections of capsaicin resulted in painful swelling that was also absent in the mutant mice.

I know what you're thinking: Thank God, someone has finally made a Tabasco-resistant mouse, now the world will be a better place. But it could prove an important discovery if you're one of the millions of Americans who suffer chronic pain.

There are other compounds involved in the pain pathway, called vallinoids, which are structurally related to capsaicin and also activate the capsaicin receptor. Vallinoid compounds are released during injury and are responsible for the pain and hypothermia generated by inflammation and certain types of tissue damage. They bind to the receptor in the same way as capsaicin, and the brain subsequently perceives pain.

But the researchers found that, when the capsaicin receptor is absent, the mice are immune not only to spicy food but also to pain caused by vallinoid compounds. They were also less susceptible to extreme heat, withstanding much higher temperatures than normal mice. But they were still able to feel pain that activated receptors other than the capsaicin receptor.

Essentially, this means the mutant mice were immune to specific types of pain, particularly chronic internal pain caused by tissue damage and inflammation.

Scientists involved in pain management are now wondering whether they can use this information and apply it to humans. For instance, if the capsaicin receptor on a nerve can be blocked and vallinoid compounds prevented from binding to it, pain will not be interpreted by the brain. Such drugs that mimic and block capsaicin receptors will have fewer side effects than current pain medications that also affect cognitive function, such as morphine. Pharmaceutical companies will be eager to build on their success with the production of new drug therapies.

So, thanks to Christopher Columbus, some brave mutant mice and the seeds and membranes of peppers, we'll soon have a novel way of treating pain. And a side effect of such treatments also will minimize the burning tongue and sweaty forehead experienced when eating spicy foods.

But, until then, hand me the Tabasco sauce and clear the room — my chimichanga's nearly ready.