This Will Hurt - And Now We Know Why - could lead to drugs that reduce pain

November 28, 2006

This Will Hurt - And Now We Know Why - could lead to drugs that

reduce pain

You might not believe it, but telling a lie can cause physical pain.

What's more there is a name for it, the nocebo effect.

It can take hold when patients are given an inert pill and told it

will intensify unpleasant symptoms. Now its biochemical pathway has

been traced - a breakthrough that could lead to drugs that reduce

pain.

In 1997, Fabrizio Benedetti of the University of Turin, Italy, and

his colleagues found that patients recovering from painful surgery

were not susceptible to the nocebo effect when given injections of

proglumide, which blocks the action of cholecystokinin (CCK), a

neurotransmitter associated with anxiety. The team have now carried

out an experiment that shows the neurotransmitter can turn anxiety

into pain (Journal of Neuroscience, vol 26, p 12014).

Forty-nine volunteers raised one forearm vertically until it drained

of blood, then a tourniquet was applied to prevent its return. With

the arm resting on the bed, they repeatedly squeezed a hand

exerciser. This would normally induce pain in the forearm that

becomes unbearable after about 15 minutes.

The volunteers rated their subjective pain every minute, and each

had blood samples taken just before the test, and at 5 and 10

minutes after it started. The samples were tested for the stress

hormones adrenocorticotropic hormone and cortisol, which serve as an

objective proxy for the level of anxiety felt.

While volunteers given a nocebo alone reported higher pain than the

control group which had received no nocebo, subjects given nocebo

plus proglumide reported pain only equivalent to the control group.

However, their blood chemistry showed much higher anxiety levels -

the same as those who received just nocebo. Benedetti says that

proglumide must stop CKK's normal function of turning chemical

signals of anxiety into exaggerated pain.

At present, proglumide is the only CCK blocker licensed for human

use, and it is not particularly effective, says Benedetti. The

Italian team is now working with drug companies to produce CCK

blockers that can be incorporated into narcotics, which will help

alleviate both physiological and psychological pain simultaneously.

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