Pain Leaves a Signature in the Brain

Boost for patients

By Carey Goldberg, Globe Staff
December 19, 2006

Researchers foresee a day when people tortured by chronic, unexplained pain will be able to prove that they really hurt -- evidence that could help sufferers be taken more seriously and could even lead to better treatments.

Recent studies suggest that prolonged, ongoing pain leaves a signature in the brain that can be detected using advanced imaging techniques. In other work, researchers at Massachusetts General Hospital and elsewhere have found that excruciating nerve damage can be detected in bits of skin the size of a pinhead. And genetic tests may someday prove useful, researchers believe: Certain genes appear to be linked to lower pain thresholds and a tendency to develop chronic pain.

Most of the research remains years from helping patients, but as it comes to fruition, "what it means is that no longer can they say, 'it's all in your head,' " said Jim Broatch , who leads an advocacy group for people with a specific chronic pain disorder.

Clinical proof of pain could make an enormous difference for patients -- emotionally, with unsympathetic relatives and colleagues, and legally, in battles with insurers and employers, researchers say.

And as science uncovers more of the objective signs of pain, that knowledge may help with diagnoses, treatment, perhaps even the development of new drugs, they say.

Late last month, German researchers reported that they had turned up microstructural changes in the brains of people who had suffered for years from lower back pain.

The study of 40 patients, presented at the Radiological Society of North America conference in Chicago, used a type of brain scanning called Diffusion Tensor Imaging, which can detect long-term changes in the nerve pathways in the brain.

The scan identified three areas involved in pain processing that showed signs of heightened activity. It was as though pathways that had started as single-lane roads had been expanded into four-lane superhighways, as more and more signals traveled along them, said researcher Juergen Lutz .

"With these objective and reproducible correlates in brain imaging, chronic pain may no longer be a subjective experience," Lutz said in a press release.

Other work focuses on the theory that people who have chronic pain might have something wrong with their pain-killing system.

Last month, University of Michigan researchers reported findings that patients with fibromyalgia, a chronic pain disorder, have abnormally low levels of natural opiate-like painkillers in parts of their brains.

The study, presented at a rheumatology conference, "also just validates that these people are in pain," said researcher Richard E. Harris . "They're trying to turn on their analgesic system but it's not enough to reduce the pain."

Brain imaging of pain is still too experimental for clinical use but that is coming, Harris said. "I'd say it will probably be five or 10 years until we can have a patient walk into a doctor's office and say, 'I have pain,' and the doctor says, 'I want to refer you out to a specialist who does imaging to verify that or find out where your pain is located,' " whether in the brain, spinal cord, or elsewhere, he said.

Proving the presence of pain through genetic testing is probably even further away , Harris and others said. Several studies have established a link between a gene and pain disorders, including one that can affect the jaw; a mutation in that same gene seems to predispose people to low pain-killing opioid activity in the brain and low pain thresholds, published research suggests.

Other work is much further along. At Mass. General, for example, Dr. Anne Louise Oaklander is already measuring "the objective correlates of pain" by counting the numbers of pain-sensing nerve endings in tiny skin samples from patients with unexplained pain. Paradoxically, patients with previously unexplained pain tend to have fewer such endings.

Such skin biopsies allow researchers to diagnose "small fiber neuropathies, " the nerve damage that is sometimes a side effect of diabetes and other diseases. The nerve endings are so tiny that they have been largely invisible, Oaklander said, but skin biopsies are "opening a window into the pain system, allowing us to see when it is damaged."

Oaklander's work recently helped a college athlete who suddenly began experiencing an unbearable burning sensation in his palms and on the soles of his feet, according to a paper slated for publication in the February issue of the journal Anesthesia & Analgesia.

Greg Palladino , a lacrosse goalie at Southern New Hampshire University, was on a team trip to Bermuda last year when he began suffering a pain that only submersion in ice would alleviate. It was as though broken glass were running through his veins, he told his doctors.

He returned home and was treated repeatedly at area hospitals for weeks. Despite extensive tests, the doctors were baffled, said Palladino's father, Steven. Medicine failed to help, and he lost 55 pounds in weeks.

When Oaklander was called in, she did a skin biopsy that showed conclusively that Palladino's "erythromelalgia" -- his red, burning appendages -- stemmed from severe damage to small nerve fibers that apparently came on because of an auto immune reaction. For some reason, his body had started attacking its own nerve cells.

The biopsy gave doctors the confidence to put Palladino on enormous doses of steroids to stop the auto immune attack, and he has almost completely recovered, his father said.

Palladino was -- in a way -- lucky that he had tissue damage that could be detected; many patients, Oaklander said, have very real pain that is caused by undetected problems in their nervous system, afflicting them with "an invisible disability that leaves no traces."

"It's a wiring problem," she said. "It's like when your oil light on your dashboard goes on, and you think, 'My car must be low on oil,' but you pull over and check your oil and it's fine, and you realize it's an electrical problem. These are people who have electrical problems in their pain system, and their neurons are firing as much as if they had a broken leg, only their leg is fine."

For patients with chronic unexplained pain, the lack of physical proof of their suffering compounds the problem, pushing some as far as suicide.

"You feel like you're malingering, you feel like you're crazy," said Mary Beth Ludington , patient representative for Jim Broatch's group, the Reflex Sympathetic Dystrophy Syndrome Association, which helps people with pain disorder. "I used to feel like a wimp until I was diagnosed. Then it was: 'Hallelujah! I'm not crazy and I'm not a big wimp! There's a reason for this, and a name.' It really validates the suffering that a lot of people go through."

Carey Goldberg can be reached at goldberg@globe. com.  

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