Doctors refining pain relief

Special to The Times

When Dr. Darlyne Johnson, 46, found out three years ago that she needed hernia surgery, she balked. "I knew what was going to happen -- I'd get sick."

Each time Johnson has had surgery over the years, she's wound up with such terrible nausea and vomiting from painkillers that she had to stay in the hospital overnight.

This time, however, 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 can make people feel sick or spacey if used as a whole-body anesthetic.

"Basically, I was pain-free," says a delighted Johnson, an obstetrician-gynecologist in South Weymouth, Mass., who immediately began referring the device to her patients undergoing C-sections.

That is just one example of doctors' increasing efforts to understand -- and manage -- pain.

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 to 75 million Americans. Another 25 million more suffer every year from acute pain after surgery or injury.

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.

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The body's reactions

Although pain is an intensely subjective phenomenon, there is growing objective evidence of how pain is registered in the brain.

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 with functional magnetic resonance imaging and found that in those reporting the most intense pain, several regions of the cortex (the outer layer of the brain) were activated more often and more intensely.

Dr. Catherine Bushnell, a professor of anesthesiology at McGill University, has found that when people are distracted from pain, scans reflect a diminished experience of pain, 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 pinprick, 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 to the brain from, say, a cut finger, injured tissues and nerves produce a slew of chemical signals, including substance P, bradykinin and glutamate. Dr. Clifford Woolf, a professor of anesthesiology research at Massachusetts General Hospital, calls glutamate "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 such as 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.

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Evolving treatments

The treatment of pain is changing too.

One example involves sensitization, or "windup" pain. When you injure nerves in your finger, nerves in the spinal cord "reorganize to amplify pain and remember it," says anesthesiologist Carr. In other words, acute pain becomes transformed into chronic pain.

To prevent this in surgical patients, some doctors now give patients COX-2 inhibitors such as Vioxx or Celebrex before surgery. These drugs block an enzyme called cyclooxygenase-2, a key player in pain transmission.

Earlier this month, researchers writing in the Journal of the American Medical Assn. 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 opiates than those who did not get the COX-2 drugs.

Other examples of successful pain management abound:

* For cancer pain, 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 increases longevity by a month or two.

* For people with neuropathic pain, antiepileptic 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 in both diabetes and shingles. Other gabapentin-type drugs are now in clinical trials for treating pain.

* For people with 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 nonsurgical techniques, such as using heated coils to destroy nerves in damaged disks.

Directly addressing the link between chronic pain and depression can also help ease pain, says Dr. Alan F. Schatzberg, chairman of the department of psychiatry and behavioral sciences at Stanford University Medical School.

An epidemiological survey of 19,000 people in Europe showed a huge overlap between pain and depression. And a study of 1,800 older people with arthritis, published in a recent issue of the Journal of the American Medical Assn., found that treating depression with drugs and psychotherapy helped with both depression and pain.

Nondrug approaches, most notably acupuncture, can be effective as well.

As for Johnson, who had hernia surgery: After the procedure, she went home quickly and needed only over-the-counter pain relievers. "It was a whole different experience."

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