The Pain Chronicles (15 page)

NEUROPATHIC PAIN SYNDROMES

Understanding chronic pain as a disease of the central nervous system sheds light on the riddle of chronic pain, solving the question of why, for many pain syndromes, there is no clear cause and why, even in pain syndromes where there is a clear-cut cause of pain, the cause bears no clear relation to the severity of the pain. Terrible osteoarthritis can be accompanied by mild (or no) pain, while mild degenerative osteoarthritic changes can cause crippling agony.

Ordinary conditions cause extraordinary pain—in some people. MRIs show only bones and tissue; doctors look at the patient’s scan and say, “Your back looks fine, the swelling is gone” or “The bone’s all healed,” and they conclude that there is no reason for the patient still to be suffering. One study indicated that a full one-third of damaged disks looked normal on an MRI; another study indicated that nearly half of patients under sixty who had visibly degenerated disks on an MRI felt normal. The problem does not always lie in the tissue and bones; it can lie in the invisible hydra of nerves that MRIs often cannot detect.

Not all chronic pain is neuropathic. There is also muscular pain, nociceptive pain (pain that stems from tissue damage or inflammation), and psychogenic pain (physical pain that is caused, augmented, or prolonged by emotional factors). Pain-causing conditions usually involve multiple types of pain. However, many chronic pain complaints, like backache, that were once assumed to be wholly musculoskeletal, are now thought to have a hidden neuropathic component. Over time, neuropathic pain leads to musculoskeletal pain. Nerve pain makes muscles spasm, which in turn interferes with normal use of the area, which causes weakness and eventually atrophy. Changes in the person’s mood and sleep and finally personality set in, and the original problem—the nerve injury—becomes harder to detect.

“There’s tremendous ignorance about neuropathic pain,” commented Dr. Clifford Woolf, a Harvard professor who is one of the world’s foremost researchers of neuropathic pain. “Most doctors don’t know to look for it.”

Many unexplained chronic pain syndromes that appear not to be coupled with any nerve injury may be a result of a neurobiological amplification of pain signals that leads to central sensitization and hyperalgesia. With IBS (irritable bowel syndrome), which causes unexplained intestinal distress, for example, the abnormality may not originate in the intestines themselves, but rather in the person’s central nervous system.

Another good example is fibromyalgia, a baffling syndrome that disproportionately affects women, the symptoms of which include chronic muscular pain, fatigue, depression, and heightened sensitivity to touch. Patients feel as if they have been “beaten up,” as one patient put it, or are achy from a flu that never goes away. The disturbance appears to reside not in their muscles, but in their nervous systems. Fibromyalgia patients have been shown to have lower pain thresholds and altered chemistry in their spinal cords and in the parts of their brains involved in regulating pain. They also suffer from a dysregulation of the neurotransmitter dopamine (which is intimately involved in feelings of well-being) and a dysregulation of the neurotransmitters serotonin and norepinephrine (which are involved in both depression and pain modulation). The predilection to develop fibromyalgia is likely to be genetic.

Although fibromyalgia has been studied since the seventeenth century, it was not formally recognized as a disease until 1987, and many physicians continue to believe it is a psychological disorder. Of the dozens of women I saw in pain clinics during my research who were suffering from fibromyalgia, every one had had the experience of being disbelieved and being asked questions such as “Are you having marital problems?” in an insinuating tone, as if that were the cause of their pain. (And many were; chronic disease usually causes marital problems.)

Dr. Richard Gracely and Dr. Daniel Clauw have examined fibromyalgia patients and patients suffering from lower-back pain that has no identified cause. In one study, they attached a small device to the base of subjects’ thumbnails that applied pulsing pressure at varying levels ranging from innocuous to painful. The investigators discovered that the subjects with fibromyalgia and back pain said they experienced mild pressure as painful, while the healthy control subjects experienced the squeeze as only slightly unpleasant.

Were those patients just—as British doctors like to say—moaners? Before the invention of functional brain imaging (a technique that allows researchers to take a video of sorts, or a 3-D movie, of the brain as it responds to pain), the question would have been unanswerable. Doctors’ impressions of patients’ credibility would have been mainly a reflection of their own personalities and whether they were inclined to believe or disbelieve patients. But in the Gracely and Clauw study, functional imaging was able to see that the patients were truthfully describing their experiences as the imaging documented activation in the pain-processing areas of the brain—activation that was not seen in the control subjects’ brains until the pressure on their thumbs was dramatically increased.

What was the pain-processing circuitry in my brain like? I wondered when I read about the study. Was there a brain imaging study I could volunteer for?

SURGICAL PAIN SYNDROMES

Surgeons warn patients of many remote risks, from blood clots to the possibility of anesthesia producing a fatal reaction, but they often don’t mention (and perhaps remain largely unaware of) the much more likely possibility of developing chronic neuropathic pain. One of Dr. Carr’s patients was a wealthy man whose life was ruined by having a nerve nicked during plastic surgery to correct protruding ears. Another patient acquired chronic chest pain after being treated in a hospital for a collapsed lung, when a tube was inserted in her chest—one of the body’s most nerve-rich areas. One poignant category of patients in pain clinics is that of those who have had surgery specifically
to treat
chronic pain, but instead, whose surgery worsened their pain, an outcome for which they say they had no warning. Pain following the common back surgery of laminectomy (which removes part of the vertebral bone and sometimes surrounding ligaments and muscles as well) is so common that it has a name (
post-laminectomy syndrome
).

The classic method of performing a thoracotomy (a chest incision that cuts through ribs to gain access to the heart, lungs, or other organs) carries a high risk of lasting pain. In one study, 30 percent of patients reported pain four years after their surgery. “If you ask thoracic surgeons,” Dr. Woolf said, “they would say, these are big life-threatening situations—heart surgery or cancer. The fact that the patient has pain for the rest of his life is not important—they feel, ‘I saved your life, what do you expect?’ Pain is not seen as life threatening. And until patients have pain, they can’t imagine what it’s like—the way it’s there all the time and makes you miserable.”

A significant percentage of cancer survivors suffer from chronic pain, stemming either directly from their tumors or from their treatment (radiation and chemotherapy can damage nerves just as surgery can). Moreover, survivors often have difficulty finding doctors willing to prescribe opioids once their pain no longer enjoys the social sanctification accorded by malignancy.

A landmark 1997 University of Toronto study by Dr. Anna Taddio and others has troubling implications about the impact of pain on infants and children. The study compared the pain responses of groups of infant boys who were uncircumcised, circumcised with an anesthetic cream, and circumcised without anesthesia. Four to six months later, the group who had been circumcised without anesthesia had the lowest pain threshold, crying longer and showing more visible signs of pain at their first inoculations, providing evidence that there is enduring cellular pain memory when damage is inflicted upon the immature nervous system.

A CLASSIC MISINTERPRETATION

At some level, every doctor is familiar with central sensitization because they know that a patient who comes in with twenty years of back pain is more than twenty times less likely to get well than one who comes in after just six weeks (a fact I wish I had appreciated before my pain settled in).

“In our clinic, we’re trying to undo eons of pain history—problems that began in the Mesozoic era,” Dr. Carr commented. “The only real cure for chronic pain is prevention. But everything from physician and patient ignorance to managed care policies of
delay, defer, deny
means that by the time a patient gets to a pain clinic, it’s late. Sometimes I wish I could send them back to their early doctors and say, ‘Don’t you see what’s going to happen to this person if you keep letting this go?’ ”

Leigh Burke complained of pain for more than a year after the surgery for her brain tumor before she was referred to a cancer pain specialist and anesthesiologist whom she liked very much. Her records do not even note whether her occipital nerve was cut, and (since the risk of chronic pain is not an issue surgeons usually consider) her surgeon may not have noticed the dental floss–size nerve. At any rate, the Nice Doctor, as she thought of him, did not investigate the nerve; what were visible to him were severe muscle spasms in Leigh’s head, neck, and shoulders.

It was a classic pain misinterpretation. He seized on muscular pain as the primary problem—the pain generator—rather than a secondary symptom, and he diagnosed tension headaches. He injected her forehead with Botox—a preparation that, when injected into muscles in minute doses, essentially paralyzes them and thus prevents spasms for a few months. Although Botox is known mainly as a cosmetic treatment for reducing wrinkles, it is increasingly being used to treat a variety of medical problems, including headaches (even migraines).

He also prescribed migraine medicines and tricyclic antidepressants (an older form of antidepressants, which are considered more effective against chronic pain than the newer SSRIs, such as Prozac and Zoloft, but have more troublesome side effects). She tried range-of-motion physical therapy, stress-reduction courses, psychiatric treatment, yoga, and meditation. She also drank a dozen cups of coffee a day—an ill-advised treatment for migraines (small amounts of caffeine help headaches; large amounts produce dependency and can create rebound headaches). The Nice Doctor steered her away from opioids with warnings about their addictive qualities. Instead, she took dangerously large amounts of ibuprofen and Tylenol.

The Nice Doctor later explained to me that he felt comfortable with anti-inflammatory drugs and uncomfortable with opioids. Yet while large doses of the drugs are sometimes needed to treat inflammation, contrary to popular opinion, for long-term use, opioids can be a safer and more effective analgesic. Certainly, when I was overdosing on Tylenol, Advil, Motrin, aspirin, and Aleve, I would have been astonished to learn that. While anything over-the-counter seemed benign, I believed the rhetoric that opioids are a “gateway drug” that turn ordinary people into tragic statistics.

Anti-inflammatories are most effective at easing the pain of—
surprise
—inflammation, which comes from injury or inflammation-causing diseases such as rheumatoid arthritis. Tylenol, which works through an unknown mechanism, is not in fact classified as an anti-inflammatory. (The effects of its basic chemical compound were originally discovered when a pharmacist’s mistake caused it to be accidentally given to a patient, whose fever was dramatically reduced.) It was introduced into the market in the 1950s, where it was a huge success, undermining aspirin’s market domination. Although Tylenol does not upset the stomach, taking the maximum recommended dose longer than the short period the manufacturer recommends can cause liver toxicity, liver failure, and even death (risks that increase greatly when these drugs are consumed with alcohol, as I used to do). The most common cause of acute liver failure in the Western world is toxicity from acetaminophen (the ingredient in Tylenol). An often-fatal disease, liver failure annually affects two thousand people in the United States. According to a 2002 study, while a majority of the patients had exceeded the daily maximum recommended dose, nearly one-fifth had not. Three-quarters of the patients were women, although it is not known whether women are innately more susceptible to acute liver failure or are simply inclined to take more over-the-counter medications.

Aleve, aspirin, Motrin, and other nonsteroidal anti-inflammatory drugs (NSAIDs), as they are called, pose an even greater problem, causing stomach ulcers in as many as one-fourth of all patients who take them on a long-term basis. Each year 6,000 to 7,500 Americans die from gastrointestinal bleeding and related complications associated with taking NSAIDs.

“IT’S HARD WORK BEHAVING AS A CREDIBLE PATIENT”

Even as they endangered her life, the massive doses of Tylenol and aspirin medications failed to reduce Lee Burke’s pain to a manageable level. Seven years—a biblical length of time—elapsed, during which she became increasingly disabled. She went from specialist to specialist—headache specialists, balance specialists, and behavioral pain-medicine specialists—and her worsening condition was met by skepticism, contempt, irritation, frustration, and pity.

Women report more frequent pain, as well as pain of greater intensity and duration, than men. They suffer disproportionately from pain-causing conditions, such as autoimmune diseases, migraines, headaches, musculoskeletal pain, and abdominal pain. In addition, they are more likely to seek treatment for pain than men are, and when they do, they present—or are perceived as presenting—more psychological symptoms. In medical literature throughout the centuries, the archetypal “problem patient” is a woman. Thus, a woman coming into the office of a male physician may find herself having inadvertently entered a highly coded complex social situation, the nature of which she may not understand and which may not serve her well.

A fascinating 2003 Norwegian study by Dr. Anne Werner, a sociologist, and Dr. Kirsti Malterud, a physician and researcher, focused on the gender dynamics between women with chronic pain and their physicians. Entitled “It’s Hard Work Behaving as a Credible Patient,” the paper detailed the ways in which women with chronic pain symptoms try to discern and comply with the hidden rules of the medical encounter in order to get the help they need. The women described struggling to present their pain in a way that others will feel is “just right”: to make their symptoms “socially visible, real, and physical” and to achieve “a subtle balance not to appear too strong or too weak, too healthy or too sick.”

The balance proves to be elusive. As in many other studies, the women provided accounts of how they were “met with skepticism and lack of comprehension, feeling rejected, ignored and being belittled,” and continually “tested” and “assessed” for psychological factors. “How assertive can patients be without appearing too strong to pass as . . . ill?” the women wondered. Although they felt they needed to be assertive in order to get referrals, pain medication, sick leave, and treatment, some of the women were working to demonstrate “appropriate surrender” and to appear to follow the doctor’s recommendations. Rather than confront their doctor with unmet needs, they often left him without saying why and paid for treatment themselves elsewhere. “You have to tread rather softly,” one woman explained, “because once you antagonize them, it’s not certain that you’re any better off.”

The women were also busy trying to achieve “appropriate appearance” because they felt—as in the case of rape—that their clothes and appearance were used to assess their credibility. “Comments such as ‘You don’t look ill’ . . . or ‘you are so young’ made them feel irritated, sad and frustrated rather than flattered.” They tried not to dress too attractively. They were concerned that if they exercised, their illness would not be believed. One woman felt she had tried too hard in a test of muscular strength and thus was seen as healthier than other patients who had tried less hard. Another woman discovered that spending time in the sun had given her too healthy a glow when the doctor greeted her by saying, “You’re not ill!” She gazed at him in stunned silence, and he changed it to, “You certainly don’t look ill!” The young women were told they were too young to have chronic pain; the middle-aged women were told their symptoms were merely menopausal.

Dr. Carr gave Lee a new medication—Neurontin—that has been found to be specifically effective against neuropathic pain. Invented as an antiseizure drug, Neurontin quiets the misfiring nerves responsible for neuropathic pain. He also told her to replace Tylenol and aspirin with Darvocet (an opioid) and Soma (a muscle relaxant).

When I called Lee four months after her appointment with Dr. Carr, she said she felt 50 percent better from a combination of Neurontin, Darvocet, Soma, and other drugs. The muscle spasms—so rigid that the Nice Doctor compared them to railroad tracks—had melted. She no longer needed a snorkel for her daily swim because she could move her head from side to side again. As with opioids, the side effects of large doses of Neurontin can be considerable. But while her headaches sometimes required so much Neurontin that she was too dazed to walk, Lee was glad to be able to sit up to watch television instead of simply lying prone in agony.

“Dr. Carr is my savior,” she said. I recalled the way she left the appointment, clasping his hand as if she wanted to kiss it and looking at him with hope so intense it was hard to watch.