This week–

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. Michael Brooks ●

This will hurt – and now we know why

12 | NewScientist | 25 November 2006 www.newscientist.com

–It’s the nocebo effect–

SAND

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AKER

/ALA

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