Will a fresh look at pain overcome drug barriers?

Barriers to understanding pain are starting to fall and scientists and drug firms say a fresh approach is producing potential new drugs to hit where it hurts.

Millions of people across the world suffer chronic pain—such as nerve, joint or muscle pain that lasts weeks, months or years—and many fail to get adequate relief, partly because doctors have a relatively scant grasp of what causes it.

But new imaging techniques, a recognition that the brain’s responses are central to pain and a growing realisation of pain’s cost to society, mean the scientific community is now pushing for it to be redefined as a disease in its own right.

As pain moves status from symptom to disease, interest among some of the biggest drug firms is picking up.

Pfizer, the world’s mightiest drugmaker, has a large pain research team working on a portfolio of drugs, some of which are generating excitement in the field.

“The science has moved on considerably,” Martin Mackay, Pfizer’s head of research and development, told Reuters.

He said new technologies allow more objective measuring of pain, adding: “Our knowledge of targets and human genetics has taken a real step forward in the last few years.”

Science is shifting attitudes too.

Irene Tracey of the Pain Imaging Neuroscience Group at Oxford University published a study last year which reviewed 10 years of imaging research and found chronic pain is linked to functional, structural and chemical changes in the brain.

So, pain is very much in the mind, and the brain’s responses to it are key to what it feels like and how long it goes on.

“Pain doesn’t exist until the brain gets hold of it. And one of the things brain imaging has been very good at is taking away some of the myths and cultural biases against pain,” she said at a meeting of experts in London earlier this month.

“Chronic pain fits the definition of a disease,” she said.

Pain, however, can be a tricky condition to medicate, as the numbers of sufferers show, and not all drugmakers are convinced it is a profitable area. Britain’s GlaxoSmithKline said last month it was cutting research in the field.

Many pain killers around today, from products like aspirin or paracetamol to opiates used for cancer pain, rely on mechanisms of action exploited since Egyptian times or were found as side effects of drugs developed for other things.

PAIN HURTS

The sheer size of the problem shows the need for more effective drugs. Pain hurts, in more ways than one.

In Britain alone, it affects about 7.8 million people, about 13 percent of the population, and a 2002/03 survey by a group called Pain in Europe estimated that as many as one in five Europeans suffers chronic pain.

Studies show that around 22 percent of people with chronic pain become depressed and 25 percent go on to lose their jobs.

Pain is estimated to cost more than 200 billion euros a year in Europe and $150 billion in the United States.

“It has huge ramifications, not only for the person themselves but also for society as a whole,” said Beverly Collett, a consultant in pain medicine at the University Hospital of Leicester in central England.

In recognition of this, the European Union’s Innovative Medicines Initiative gave some of its first grants to pain researchers to work with pharmaceutical firms to try to speed up the process of finding new drugs.

Steve McMahon, director of the London Pain Consortium, said his group and several others in Europe were now working with about 10 major drug companies to push the field forward.

PAIN PIPELINE

Among the most promising drug prospects is tanezumab from Pfizer, which McMahon says is “the first drug in a long time to have originated from basic science identifying the biological problem and suggesting a therapy.”

Pfizer’s MacKay is naturally upbeat about the experimental medicine—an antibody currently in late-stage trials for osteoarthritis caused by wear and tear of the joints. He named it among the firm’s top picks for “blockbuster potential”.

McMahon hopes it will be the first of many.

Another potential from Pfizer is a drug based on work by British scientists who identified a genetic mutation several years ago that prevents those who have it from feeling pain.

The gene clue was found in a Pakistani boy—and members of three related families—who had become a local celebrity as a street performer, stunning crowds by plunging knives through his arms and walking on burning coals.

The experimental drug seeks to mimic the gene mutation and block a sodium channel which normally produces nerve impulses that convey pain signals to the brain.

“This is the way that pain (research) is going to go now, where you have very strong human genetic evidence and you’re able to mount really large campaigns against tough targets and then take them through to the clinic,” MacKay said.

For Tracey, scientific progress will only keep its momentum if society agrees pain is something scientists should fight.

“You can still hear it in the language, with expressions like ‘no pain no gain’,” she said.

“These are real barriers that we have to get over in society if we’re really going to accept that we should be treating pain and putting more money into it.”

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By Kate Kelland

LONDON (Reuters)