Putting pain in its place

Dr. Darlyne Johnson, 46, an obstetrician-gynecologist at South Shore Hospital in South Weymouth, is no stranger to pain -- and not just the pain of other women having babies.

Over the years, Johnson had surgery twice, and both times, wound up with such terrible nausea and vomiting from painkillers that she had to stay in the hospital overnight.

Not surprisingly, when she found out three years ago that she needed hernia surgery, she balked. "I knew what was going to happen -- I'd get sick."

Then she heard about a device called ON-Q. It consists of a tiny tube, placed in the incision and connected to a small container of local anesthetic worn outside the body. Like water through a soaker hose, the medication, usually lidocaine, oozes into the wound for several days. The idea is that by blocking pain at the site of injury, patients should need smaller doses of opioid painkillers, which act on the whole body, often making people sick and spacey.

"Basically, I was pain-free," said a delighted Johnson, who immediately began offering ON-Q to her patients undergoing C-sections.

As they develop a better understanding of what causes suffering, doctors are increasingly successful at managing pain -- both the acute form, often caused by surgery or injury, and chronic problems, stemming from anything from diabetes to a bad back.

Chronic pain, which can be caused by damage to nerves (as in shingles or diabetes), inflammation (as in arthritis), and diseases (such as cancer), is a fact of life for 50 million Americans, according to some estimates, and as many as 75 million Americans, according to the American Pain Foundation, a consumer group. Another 25 million more suffer every year from acute pain after surgery or injury.

A study published in last week's Journal of the American Medical Association showed that 13 percent of the American work force experiences a loss of productivity in any given two-week period because of pain.

At its essence, pain "is an unpleasant and emotional experience associated with tissue injury," says anesthesiologist Dr. Daniel Carr, professor of pain research at Tufts-New England Medical Center in Boston. People can also feel pain when there is no obvious tissue damage, as in fibromyalgia, or after a limb has been amputated.

Pain, obviously, is an intensely subjective phenomenon. But there is growing objective evidence of how pain is registered in the brain, too.

In one recent report, Wake Forest University School of Medicine researchers subjected volunteers to pain (heat) on their skin and had them rate it on a scale of 0 to 10. They also scanned the subjects' brains and found that in those reporting the most intense pain, several regions of the outer layer of the brain (the cortex) were activated more often and more intensely.

Dr. Catherine Bushnell, a professor of anesthesiology at McGill University in Montreal, has used brain scans to show that when people are distracted from their pain, they feel it less acutely -- suggesting that a person's psychological state can change the way pain is processed in the brain.

On a more technical level, pain comes in several forms.

Nociceptive pain is triggered by tissue injury, including strong, noxious stimuli from the outside world, such as a pin prick, heat, or cold, as well as internal threats such as a kidney stone, obstructed bowel, or infection. Neuropathic pain is caused by damaged nerves. Inflammatory pain is caused when joints or other tissues become swollen and release a cascade of natural, but harmful, chemicals.

During transmission of pain signals from, say, a cut finger, to the brain, a slew of chemical signals is produced by injured tissues and nerves, including substance P, bradykinin and glutamate, which Dr. Clifford Woolf, a professor of anesthesiology research at Massachusetts General Hospital, calls "the star of the show."

At normal levels, glutamate is essential to the functioning of the nervous system; in excess, it can be devastating.

When excess glutamate over-stimulates certain receptors on spinal cord neurons (called NMDA receptors), acute pain can be transformed into chronic pain. Some drugs already on the market such as ketamine and dextromethorphan can block this process.

Researchers now know that not only do all cells, including nerve cells, have ion channels through which substances like sodium and calcium move in and out, but that particular subtypes of sodium channels govern the transmission of pain. "Some sodium channels are specific to pain fibers," says Woolf. This means that drugs targeted at only these channels could block pain without affecting other cells.

The growing understanding of pain is affecting the way it is treated, says Dr. James Rathmell, chairman of the committee on pain medicine for the American Society of Anesthesiologists and a professor of anesthesiology at the University of Vermont Medical College in Burlington.

One example is sensitization, or "wind up" pain. When you injure nerves in your finger, nerves in the spinal cord "reorganize to amplify pain and remember it," says Carr of Tufts. In other words, acute pain neurologically becomes transformed into chronic pain.

To prevent this in surgical patients, some doctors now give patients COX-2 inhibitors like Vioxx or Celebrex before surgery. These drugs block an enzyme called cyclooxygenase-2, a key player in pain transmission. Just last week, researchers writing in the Journal of the American Medical Association reported that patients undergoing knee replacement surgery who were given a COX-2 inhibitor several hours before and for five days after surgery had better pain control and needed fewer opiate medications than those who did not get the drugs.

At the Johns Hopkins Hospital, anesthesiologists Dr. Lee Fleisher and Dr. Christopher Wu are studying ON-Q in prostate surgery patients. "We are very interested in seeing if there is a benefit to blocking pain up front and never getting `wind up' pain," says Fleisher.

There's no need to convince Dr. Darlyne Johnson of that. After her surgery, she went home quickly and needed only over-the-counter pain relievers. "It was a whole different experience," she says.

Judy Foreman is a freelance columnist who can be contacted at foreman@globe.com.

New treatment techniques

The latest treatments for pain caused by . . .

Labor: Low doses of morphine injected into the intrathecal space around the spinal cord.

Cancer: Doctors implant a permanent catheter (tiny tube) into the intrathecal space and attach the tube to a morphine pump placed in the abdomen. A major Johns Hopkins study showed that this technique not only provides dramatic pain relief, but increased longevity by a month or two.

Nerve damage: Anti-epileptic drugs such as Neurontin (gabapentin) are showing promise. The rationale is that the body produces the same cascade of harmful chemicals during both the "electrical storm" of partial seizures and in neuropathic pain. Two 1998 studies showed that gabapentin can reduce nerve pain associated with both diabetes and shingles. Other gabapentin-type drugs are now in clinical trials for nerve-related pain.

Back pain: Microsurgery to remove damaged disks in the spine can improve pain control significantly, says Dr. Michael Ferrante, director of the UCLA Pain Management Center and co-director of the UCLA Spine Center. So can non-surgical techniques such as heated coils to destroy nerves in damaged disks.

Depression: An epidemiological survey of 19,000 people in Europe showed that there is a huge overlap between pain and depression. Anti-depressants that boost both serotonin and nor-epinephrine, neurotransmitters in the brain, seem to help with both pain and depression. A study of 1,800 older people with arthritis published in last week's Journal of the American Medical Association also found that treating depression with drugs and psychotherapy helped with both depression and pain.

JUDY FOREMAN