Pain Killers

Cynthia Hildt, a 64-year-old retired schoolteacher diagnosed with degenerative disk disease at age 17, spent the better part of four decades seeking relief for the intractable pain that all but ruined her life. Beginning in her twenties, she underwent several operations, some in which disks were removed and vertebrae were fused; ultimately, she says, there was no more surgery to do, and the pain “just got worse and worse.” Struggling to continue working, she sought help from doctor after doctor, with no luck. “They were all afraid I’d become an addict,” she remembers. “One doctor actually gave me a prescription for three tablets of Percocet, which isn’t even enough for one day. I almost threw it at him, I was so mad.” Ultimately, she was forced to go on disability.

In 1998, she found her way to Beth Israel Medical Center’s Department of Pain Medicine and Palliative Care. Housed in a nondescript redbrick building on Union Square East, it’s the only fully separate hospital department of its type in the country, where treating pain is on a par with curing disease. It is the creation of Dr. Russell Portenoy, who put Hildt on a potpourri of medications ranging from morphine tablets to a narcotic lollipop.

“We’re still trying to find the best combinations,” says Hildt. “But I feel like a different person. My whole life has turned around.” Though she walks with crutches and is facing knee surgery soon, she’s getting out again and enjoying her life. “I don’t feel so helpless and hopeless now. I can’t tell you how many times I thought of suicide before. It was just torture.”

Portenoy’s work is predicated on the notion that pain, rather than being an ancillary and ignorable symptom of some “real” problem, deserves recognition and treatment, whatever the source, whether it’s fixable or not, by just about any means available. To a patient, this may sound like a given, but in truth, it’s a radical departure. Historically, pain hasn’t rated high on the medical priority list. “It’s not part of medical culture,” explains Portenoy. “Doctors aren’t trained to assess subjective complaints like pain. We like to look at X-rays and lab values and see numbers and view them as objective evidence. We’re uncomfortable with the subjective.”

There are additional barriers to treatment as well. Many medical schools still don’t place much priority on pain, for example, and most insurance companies are set up to reimburse technology, not the time-consuming doctor-patient sessions often required to diagnose and treat each individual patient’s problem.

“The vast majority of patients with chronic pain,” says Portenoy, “never see pain specialists.”

“Understanding pain takes time,” says Dr. Scott Fishman, chief of the division of pain medicine at the University of California-Davis and author of The War on Pain. “And since doctors don’t get reimbursed for spending time with patients, it makes it more likely that there are patients out there who aren’t getting appropriately treated.”

All of which, pain experts insist, is shortsighted. Pain is best treated early, though it rarely is. What’s more, un- or undertreated pain often has consequences as grave as untreated disease, from longer hospital stays and rehabilitation to poorer healing, a depressed immune system, chronic pain and depression, lost time at work or being fired, and a higher incidence of suicide. As many as 50 percent of all dying patients are undertreated for pain, robbing them of their last remaining time with family and friends.

“Despite enormous strides in our ability to treat pain,” says Portenoy, “the vast majority of patients with chronic pain never have the opportunity to see pain specialists.”

But the tide finally has begun to turn toward conquering pain and overcoming the mind-set that prevents its effective treatment. With new theories about what causes it, better understanding of molecular biology, and improved technology, pain is losing its symptom status and emerging as a treatable entity in its own right, complete with its own societies (the American Pain Society and the American Academy of Pain Management, to name just two) and a proliferation of new tools and treatments.

Nowhere is that change more evident than in the pain-treatment center and hospice at Beth Israel. Portenoy – one of only four doctors in Manhattan whose primary specialty is the treatment of pain – oversees a staff of eight doctors, two psychologists, a social worker, seven advanced nurse-practitioners, and some 550 patients who have been sent there by their doctors and, in many cases, by other hospitals (despite the fact that there are top pain specialists and treatment facilities at St. Luke’s-Roosevelt, St. Vincents, Mount Sinai, NYU Medical Center, and, particularly for cancer patients, Memorial Sloan-Kettering). Even so, Portenoy concedes, the majority of his patients come not at the outset of pain but after lengthy, typically ineffective treatment elsewhere, or none at all. And many of them come even though their insurance won’t pay for treatment because so much of what takes place there is time-consuming, not to mention experimental.

What scientists have known for a long time is that the sensation of pain is conveyed from the site of injury via electrical impulses that hop from one nerve cell to the next, ultimately climbing the spinal cord to the brain, where the sensation is interpreted. What they have come to know only recently, however, is that there is a certain malleability in our nervous systems – the science-speak term is “plasticity” – that makes the process much more complex than anyone ever realized.

“We used to think that when you injured yourself there was a signal sent into the nervous system, and when the injury healed, the signal stopped,” explains Dr. Richard Payne, chief of pain and palliative care at Sloan-Kettering. That, it turns out, isn’t always true. “If the pain is allowed to go on, it’s possible for the nervous system to remodel itself,” Payne continues, “to have changed itself in such a way that there is going to be ongoing pain even if the injury has healed.”

What’s more, say pain scientists, we now know why morphine, the standard by which all other analgesics are measured, and which blocks pain by glomming on to one type of receptor, isn’t the panacea we’ve thought. The nervous system probably uses hundreds of different chemical messengers (neurotransmitters) and receptors (the loading docks on the surface of neurons where these messengers’ pain signals are received) to convey pain sensation. (You’ll soon be hearing a lot about new drugs to block both a spinal-cord receptor called NMDA and a neurotransmitter called Substance P.)

On one hand, the new knowledge explains why pain, especially long-term chronic pain, is often so hard to treat. But researchers also now have a slew of new information to work with and targets at which to aim. In the meantime, the task at hand has been to learn how to work with existing pain-treatment tools to deliver the best pain care possible while developing new ones that fit better, conceptually, with the new discoveries.

One approach that continues to gather steam is to improve the means of delivering pain killers into the system. The first example of this was patient-controlled analgesia (PCA), the now ubiquitous system that first emerged in the mid-eighties, which allows a post-op patient to manage pain relief by pushing a button that triggers the release of a bolus of morphine through his or her IV bag. PCA soon spawned other novel drug-delivery tools, including transdermal patches (some of which may soon be enhanced with electrical current, the better to drive drugs into the system more thoroughly). There are also new time-release versions of a wide range of narcotics in varying doses; tiny high-tech pumps that, when implanted under the skin, can be programmed to trickle a set dose of pain medication into the spine; a narcotic-infused lollipop (the mucosal surface lining the inside of the cheeks expresses drugs directly into the bloodstream); and the pièce de résistance, a morphine inhaler that’s currently near FDA approval. The lollipop works nearly as fast as IV morphine, the inhaler faster, according to Fishman.

Another avenue for researchers is exploring new uses for existing drugs. Doctors like this approach because it gives them immediate tools – drugs don’t have to be reapproved by the FDA for such “off-label” use. The payoff thus far:

* Epilepsy drugs like gabapentin, topiramate, and carbamazepine, known to stop seizures, seem to have a similar effect on chronic pain such as that associated with diabetes and shingles.

* Clonidine, an alpha-2 agonist used to treat hypertension, binds to alpha-2 receptors and has also been useful in treating chronic pain.

* Dextromethorphan, the key ingredient in over-the-counter cough syrup, also helps block one type of receptor that seems to be associated with chronic nerve pain. It’s being tested for use in a solution with morphine.

* Botulinum toxin, a diluted version of the toxin that causes botulism, has approval for treatment of dystonia, a cluster of disorders characterized by painful muscle spasms often associated with chronic pain, when it is administered by injection.

And then there are the new drugs – those that have arrived, and those still in the pipeline. Celebrex and Vioxx, for example, which work like aspirin but without as many gastrointestinal side effects, have been a major breakthrough – particularly for arthritis sufferers, a large component of the chronic-pain population.

A wide net also has been cast for drugs found specifically to block receptors like NMDA and neurotransmitters like Substance P. A number of prospects are either being culled from nature – the skin of an Ecuadoran frog, for example – or being built, molecule by molecule, in labs and are currently being tested in animals and humans. The most anticipated arrival is a new calcium-channel blocker; the as-yet-unnamed drug (code-named SNX-111), derived from a poisonous sea snail native to the Philippines, is in the last phase of clinical trials before submission for FDA approval.

There are also procedures designed for those who can’t get relief by any other means. One involves giving injections that will either disable or kill problematic nerves. (Among the more popular new agents being tested is capsaicin, derived from hot chili peppers.) Other prospects use the relatively gentle electricity of radio-frequency waves. In one increasingly popular procedure, a fine wire filament is surgically inserted into the spine and connected to a pacemaker-like device implanted under the skin, then programmed to periodically buzz the wire with radio waves. “It jams the pain signals,” says Fishman. “It’s like what they do in wartime to the enemy’s radio transmissions.”

One variation on that theme is the specialty of Dr. Emile Hiesiger, a neurologist and pain specialist at New York University Medical Center. Using a hollow needle, he threads a fine electrode into the spine, briefly wrapping it around specific offending nerves and heating it to nearly 180 degrees using radio waves. “In some cases it destroys the nerves; in others it partially destroys them,” says Hiesiger. “We don’t fix the problem that’s causing the pain, we just find the telephone lines that connect the pain impulses to the brain and cut them.”

For Stephen Jones, a 39-year-old Floridian who designs roof and floor trusses for houses and commercial buildings, that was more than sufficient. His sciatica pain had gotten so bad, “the only way I could be comfortable was to lie on my stomach on the floor,” he recalls. “That’s all I could do. It affected everything.” Hiesiger’s procedure dulled his pain. “I’m smiling again,” says Jones, albeit cautiously. “I had a lot of letdowns before.”

“Say you have a patient with low-back pain spreading down their leg,” says Dr. Steven Richeimer, medical director of the Richeimer Pain Institute at St. John’s Health Center in Santa Monica, California. “If you look for the seed of the problem, you may find a disk in the lower back that’s bulging and irritating a nerve. But that may have triggered a lot of reactive muscle spasms, and that will be the next layer. And then that person may be under a lot of stress, and stress will increase muscle tension, and that will make their awareness of pain more sensitive, which will in turn lower their pain threshold,” he says. “And if these problems aren’t addressed, the patient is going to get depressed as well, which can also magnify the pain experience.”

The search for anti-pain drugs has led to Ecuadoran frogs and poisonous Philippine sea snails.

“Pain is a sensory experience – but it can be magnified by something like depression, or panic attacks, or stress, or a combination of all of these,” agrees Fishman, a colleague of Richeimer’s. “You really can’t treat patients without considering their mind and body. It doesn’t mean that every patient has to be psychoanalyzed, but it does mean you have to take a kind of holistic approach.”

Which is why pain doctors have the unusual distinction of being among the few medical specialists who actually embrace alternative therapies such as biofeedback, hypnosis, and meditation. Most patients treated by pain specialists these days are encouraged to use whatever mind-body approach seems to help them relieve their pain.

Glimmers of change in the system are also evident in legal innovations to patients’ pain-related rights. California, for example, just passed legislation making pain the fifth vital sign – after pulse, blood pressure, temperature, and respiratory rate – and requiring that doctors get pain-management education before they can get their licenses renewed. A third component of the legislation mandates more such education in the state’s medical schools. Many other states are considering similar laws, and making pain the fifth vital sign will soon be routine in Veterans Administration hospitals.

What’s more, the Joint Commission on Accreditation of Healthcare Organizations, a nonprofit group that rates hospitals, drew up new standards for pain care, effective January 1, 2000, explicitly recognizing a patient’s right to accurate assessment of pain and follow-up on treatment for it. In order to remain competitive, most hospitals will be forced to comply by creating their own pain departments and centers.

Individual doctors, too, may feel increasing pressure. In a recent precedent-setting Oregon case, a doctor was censured by the state medical board for underprescribing pain medication for cancer patients. In states where medical boards can’t be induced to censure, there are a growing number of lawsuits against doctors, often filed with the help of patient-advocate groups.

Needless to say, the health-care profession as a whole has still not entirely embraced the goal of overcoming what pain specialists like to call “barriers to care.” Those barriers were built into the system long ago: In 1914, the federal government enacted the Harrison Narcotics Act, having been spurred by the number of people addicted to inexpensive, over-the-counter potions like Hooker’s Wigwam Tonic, which were liberally spiked with potent narcotics. The act separated opium-derived pain killers – morphine, codeine, and heroin – from common analgesics; thus were born “controlled substances.” Doctors who prescribed them were to be (and still are) closely monitored, and those whose patients became addicted or died prematurely risked losing their medical licenses.

As a result, narcotics were, and often still are, routinely underprescribed for both dying patients and those with chronic pain, although they are often the most effective means of helping both. Research has shown that while pain patients may become physically dependent on narcotics to relieve pain, they do not tend to develop aberrant, compulsive, drug-seeking behavior – the hallmarks of the largely behavioral and psychiatric disorder known as addiction.

“With addicts, their quality of life goes down as they use drugs,” says Fishman. “With pain patients, it improves. They’re entirely different phenomena.”

But try telling that to most doctors. Even those who understand the differences are still afraid, and with good reason. Every state enforces the Harrison Act with its own tracking system, and copies of all narcotics prescriptions are filed with the Drug Enforcement Agency.

“Half the neurologists I know don’t even bother to carry the narcotics prescription pad,” says Hiesiger. In fact, in a 1998 survey of all licensed physicians in New York commissioned by the New York commissioner of health on barriers to good pain care, 70 percent of respondents said they were unlikely to prescribe a controlled substance because of fear of being scrutinized by the authorities.

The pain docs call for more education in medical schools, for starters, as well as continuing education for those long out of school. Insurance companies need to make new reimbursement categories for pain. The government – not just pharmaceutical companies – needs to recognize the specialty and sponsor more research. And patients, say experts, need to be educated as well.

“Patients want to be perceived as good patients,” says Portenoy. “There’s this stoicism in the American character, so they don’t talk about pain as much as they should.” He cites a recent survey by the American Pain Society that found that only 25 percent of patients with moderate or worse chronic pain ever get referred to a pain specialist.

“I’m optimistic that we will have a much more clearly defined niche in the future,” says Portenoy. “But pain management as a specialty is also in a very uncertain time right now, as we face questions about the health-care system and reimbursement and how it fits into the managed-care world. How much precedence will be given to general care versus specialists, for example, and what specialists will be considered essential, and how will people get to them?

“My sense,” Portenoy predicts, “is that the next five years, when a lot of these decisions get made, will be a critical period.”

Pain Killers