Harvard Gazette





Two years ago, Clifford Woolf and some colleagues discovered that chili peppers and the burning pain of arthritis have something in common. Capsaicin, the chemical responsible for the "hot" in peppers, acts on a protein that also responds to the heat and high acidity associated with painful inflammation in the joints and skin.

Recently, the Richard J. Kitz Professor of Anesthesia Research at Harvard Medical School hit on the idea of using the same irritating chemical to "burn" people who illegally use pain medications. When an abuser of a medication like OxyContin snorts, chews, or injects the drug, he or she would get intense hot pain instead of an expected happy high. A patient taking the same capsaicin-laced pill could get needed relief and avoid unpleasant sensations simply by swallowing the pills whole, as directed.

"If a formulation containing capsaicin is swallowed whole, release of the irritant in the stomach and small intestine would not cause discomfort," Woolf maintains. "The majority of the capsaicin would be cleared by the liver on first pass."

Those who obtain opium-based drugs, including morphine and methadone, by theft or subterfuge usually crush the pills and snort or chew the powder to get "high." Laced with capsaicin, such a snort or chew would produce intense pain.

"Imagine snorting an extract of 50 jalapeno peppers and you get the idea," Woolf says. "On a one to 10 scale, the pain is about a thousand. It feels like a mininuclear explosion in your mouth. It does not harm you, but you never want to experience that feeling again."

"Moreover," Woolf adds, "inhalation of the capsaicin elicits a powerful cough reflex and severe pain if it leaks into certain tissues after an intravenous injection. In human volunteers, intravenous administration of capsaicin produces a widespread burning feeling of the chest, face, rectum and extremities as well as paroxysmal coughing." Otherwise, capsaicin appears to be safe.

Woolf thus sees capsaicin as one possible way to stem the rising tide of abuse of opium-based painkillers. "Such abuse is now a major societal problem, with an incidence that appears to exceed the use of street narcotics such as heroin and cocaine," he told a meeting called the Research and Policy Forum in Washington, D.C., on Dec. 15.

Turning off pain

Capsaicin works by hitting on a protein known as TRPV1, which transports its fiery message into the nervous system via sensory nerves in the mouth and other areas. TRPV1 also is activated by the heat and acidity produced by arthritis and other inflammatory conditions.

"Finding this out helps us to understand why these inflammatory conditions increase pain and sensitivity to heat," Woolf says.

Production of TRPV1 is controlled by an enzyme called p38, located within the sensory nerves. p38 acts like a faucet - turn it on and it can cause a 20-fold increase in the amount of TRPV1 in the skin. That's the kind of increase that will get anyone's attention.

It immediately became obvious to Woolf and his colleagues at Massachusetts General Hospital that finding a compound to turn off the p38 faucet would block any increase in TRPV1 and turn down the sensitivity to pain. In other words, this could be a new way to treat the pain felt by people who suffer from arthritis and many other diseases and conditions that involve inflammation.

Other approaches are also available. Drugs might be developed to block TRPV1, the capsaicin receiver, and several pharmaceutical companies are looking into this possibility.

Curbing abuse

Woolf has also had discussions with drug-makers about developing capsaicin-based compounds to deter the abuse of pain relievers. "It is only a relatively trivial task to formulate a product that would not release active capsaicin to patients taking the drug legally, that is, swallowed whole," he notes. "But the capsaicin would be released if the drug is crushed, injected, or chewed."

This same approach, Woolf points out, could be used for curbing the abuse of stimulants, such as amphetamines or Ritalin. The later drug is used legitimately for treating attention deficient disorder.

There is one thorny issue to deal with, however. Who would bear the cost of developing a drug that has no benefit to a legitimate user? Patients who take a drug like morphine in the prescribed fashion for relief of pain would get no benefit from the capsaicin. Therefore, development might have to be done by a government agency, such as the National Institute of Drug Abuse.

"Doing this could result in a large indirect benefit to patients," Woolf points out. "The stigma of taking narcotic drugs would be removed. It should be easier to get such medications prescribed by doctors who are currently terrified of being accused of over prescribing narcotics. And, pharmacies would be at a lower risk of theft and robbery.

"The biggest benefit, though, will be to society as a whole, because pain medicine abuse now is such a massive epidemic."