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Better Analgesia Ahead?
Pain, Though Ubiquitous, Still Poorly Understood, Say Panelists

By Rich McManus

Photos by Bill Branson

On the Front Page...

It might pain people to know that most of what today's physicians have to offer in the way of pain relief has been around for thousands of years. But a panel of four leading pain research scientists told a STEP Forum on "Pain" Apr. 22 that help is on the way as modern molecular biology teases out, on a cellular level, how pain is sensed, transmitted and experienced within the central nervous system and the brain. All four expressed cautious optimism that the future, in terms of pain management, will be more tolerable than the past — mainly due to advances in basic benchwork and in clinical research that, as one scientist said, will "finally explore what it is exactly that our patients are suffering from."


The forum, part of the staff training in extramural programs (STEP) series on current controversies in medicine, began with difficult personal testimony from Michael Price, a Washington, D.C., native now retired from a successful insurance career, who spent a portion of his life addicted to painkillers. Clearly reluctant to revisit the topic, Price recounted early encounters with the health care system — an appendectomy, a broken leg — that acquainted him with two perspectives: first, men should be tough guys who don't acknowledge hurt, and second, boy, does that Demerol do the trick!

Price said he self-medicated through much of his adult life, thinking he was smart enough to handle an addiction made easier to manage by the fact that he was self-employed, and immensely self-confident. But eventually he hit bottom, even though he felt so guilty that "I didn't think I deserved treatment...I didn't know how to ask for help, until I hurt bad enough."

Michael Price tells personal story of addiction pain.

He concluded, "There is help out there — it might take a trip to the emergency room, or the threat of suicide to get it, though...The stigma attached to addiction is pretty scary. I hope there will be other avenues in the future. But [treatment] is not worth a damn if you don't want it. Addicts," he declared, "are not bad people trying to be good, but sick people who are trying to get better."

It has only been within the past quarter century that pain studies have risen to legitimacy in their own right, said Dr. Patrick Mantyh of the departments of preventive sciences, neuroscience and psychiatry at the University of Minnesota. "Until 20 years ago, every [medical] specialty felt like they were the pain specialists." Not very long ago, pain was thought to be more a spiritual than medical burden, added Dr. Nathaniel Katz of the department of anesthesia at Harvard Medical School. "The concept of pain was medicalized only recently — for thousands of years before that it had essentially a spiritual component," Katz said. "The 'pain movement' has only been around for 25 years or so." Katz added that medicalization of pain has not been without cost; "I think we have also lost something critical to a full understanding of pain by viewing it solely as a medical problem."

Pain's rising status as a medical subspecialty has paralleled science's understanding of how it actually works, which Mantyh elucidated at the level of the body's 2 million afferent, or sensory, neurons — some as long as 2 or 3 feet — capable of reporting noxious stimulation, or nociception, back to the brain. Fully 80 percent of the body's sensory fibers are involved in nociceptive signaling, he said. That's because pain detection, or what he called "the gift of pain," is so essential for an organism's survival, serving a critical guarding/protective function.

Speakers at the pain forum included (from l) Dr. Nathaniel Katz, Dr. James Zacny, Dr. Christine Miaskowski, Dr. Patrick Mantyh and Michael Price.

"You can't have pain without the brain," he remarked, underscoring the cortex as the seat of both the sensation of pain, and of the body's response to it, in what he termed ascending and descending feedback loops.

Science has made remarkable progress in finding and characterizing the channels that convey noxious stimuli, Mantyh reported. Researchers can now image the neurochemistry of pain, and have found that the nervous system is very plastic; it's capable of both amplifying (as in chronic cancer pain), and of ignoring (as when a wounded soldier doesn't even realize he's been hit until after he's rescued a buddy on the battlefield) pain signals.

"There is enormous difference in how pain is experienced by an individual, based on gender and past experience," said Mantyh, whose point was later echoed by Dr. Christine Miaskowski, professor and chair of the department of physiological nursing at the University of California, San Francisco; her work has shown enormous disparities in the way pain is assessed and managed in a variety of populations, depending on sex/gender, culture/ethnicity, and age, particularly the elderly and infants/children.

"The central nervous system of someone in chronic pain is different from the CNS of a normal person," Mantyh said.

Pain authority Mantyh

"Our knowledge of [how the current crop of analgesics work] is woeful," Mantyh continued. From the morphine-based drugs, to NSAIDs (nonsteroidal anti-inflammatory drugs) to such new preparations as gabapentin and neurontin, "we know virtually nothing about where these drugs act." He called for more disease-based animal models of pain, and increased education among health care professionals about the limits and promises of pain management.

Harvard's Katz noted that "pain is ubiquitous — it's all over." It resulted in 40 million visits to doctors' offices in 1981 for new instances of acute pain, and 167 million visits in 1995 for new and standing incidences. More than 4 billion work days were lost to pain in 1985, he showed.

He said there is evidence from the year 300 B.C. of the dangers of opiate addiction in medical therapy, proving that morphine has long been familiar to the healing arts. He lamented that even today, "There is no prospective study yet of the opioid addiction rate post-treatment." He added, "The pharmacopeia available to physicians today is virtually the same as that available at the time of Weir Mitchell (a Philadelphia physician and writer who treated Civil War casualties) in 1864, which was in turn virtually identical to what was available at the time of Christ." Why, he wondered, has there been no success to date in developing a single new rationally designed analgesic? He suggested this could be an important field for NIH to seed, along with studies of how to reduce common side effects of analgesics.

"We do a lot more caring than curing when it comes to chronic pain," he said, calling for "compassion, humility and pragmatism" in assessing pain in the clinic. "Under-treatment is generally a far greater problem than over-treatment."

Addressing the bedrock practicalities of getting help for pain was Dr. James Zacny of the department of anesthesia and critical care at the University of Chicago. His research has asked, Can patients who are on opiates for their pain drive vehicles safely, remain employed and avoid the risk of turning into addicts themselves? The answers, though riddled with caveats, are largely affirmative; people taking opiates for their chronic pain generally are able to operate vehicles as safely as unmedicated peers, can continue to be productive on the job and only rarely succumb to addiction.

Almost all of the speakers, despite their penchant for hard science, shared a personal dimension of pain, testifying to its force in shaping human experience, from moderator Dr. Alan Willard, chief of the Scientific Review Branch at NINDS, who said the forum's planning committee could not avoid discussing their own problems with it (especially the "episodes not necessarily appropriately treated") to Harvard's Katz, who was bedridden with back pain in the days prior to the forum, to UCSF's Miaskowski, who said her decades of involvement in the field stem from seeing her dad die in "intractable pain," thus motivating her to spend a career improving the situation. The power to treat pain — one of the most welcome weapons in the physician's armamentarium — prompted Mantyh to conclude, "You can return life to a patient when you can relieve their pain."

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