The Pain Chronicles (21 page)

THE WONDERFUL DREAM THAT PAIN HAS BEEN TAKEN AWAY FROM US

How can such a syndrome be prevented? Dr. Woolf has some ideas about molecular agents he believes may be critically involved in inciting or sustaining neuropathic pain. For example, he said, in animal models there are certain abnormal sodium ion channels that appear and become activated only in the damaged sensory neurons. There are also sodium channels involved in inflammatory pain that help determine the excitability of nerve fibers or pain fibers in the vicinity of the damaged tissue. If the critical molecular components in different types of chronic pain could be identified, then an antagonist might be found and introduced as a drug.

Would “the wonderful dream that pain has been taken away from us,” which was trumpeted at the invention of anesthesia, finally, then, be true? Would such a drug help all the people who already have this pain—or only prevent others from developing it? Can the cortical reorganization be reorganized, the gray matter un-atrophied, the damage to the central nervous system repaired? After all, neuroprotective drugs can’t protect neurons that have already died, and neurons cannot regenerate. What about Lee Burke, and the babies circumcised without anesthesia? What about me?

Dr. Woolf looked at me and hesitated, as if wondering just how unwelcome the news would be. “We don’t really know,” he said tactfully. Another pause. “Not in the present state, no.” But even if the damage cannot be undone, he pointed out, treatment might still help suppress the abnormal sensitivity. “But obviously it’s going to be much easier to prevent the establishment of abnormal channels than to treat the ones already there.” He rested his head against his hand. “Obviously.”

I glanced out the window and tried to make out the shapes of the ships in the harbor through the rain. But just then pain radiated down my shoulder and into my hand, so swiftly I dropped my pen on the tabletop. I thought of the Righteous Sufferer.

Head pain has surged up upon me from the breast of hell . . .
A demon has clothed himself in my body for a garment . . .

I asked about pain’s relationship to meaning.

Dr. Woolf blinked, surprised, and then scrunched up his face as he recalled a lecture given to the Harvard Medical School by Divinity School faculty on the religious meanings of pain.

“Imagine how foreign that point of view was to me,” he said, shaking his head disapprovingly at the memory.

“But pain feels meaningful,” I suggested timidly, “like a riddle or a dream.”

“That’s crazy,” he said forcefully. “That’s like the myths about TB we were talking about. Chronic pain is not some”—he searched for the right word—“
code.
It is a terrible, abnormal sensory experience, pathological activity in the nervous system.”

Could these science terms, still so foreign in my mouth, become mine? Could the demon that clothed itself in my body turn into excitotoxicity and overuse atrophy? Cervical spondylosis and spinal stenosis and impingement syndrome—if I truly believed that’s what it was and that’s all it was—would be far less alarming than a curse, a punishment, a private sorrow, a symptom of aloneness, an inexplicable blight, or any of the myriad unhappy ways I understood and experienced and expressed my condition.

Would it also be less painful?

Seven years later, Dr. Woolf—newly appointed director of the neurobiology program at Children’s Hospital in Boston—was replete with good news. His group had recently discovered a drug combination they are working on to develop into a pain-specific local anesthetic—an anesthetic, that is, that would act only on pain nerves and not affect the motor and autonomic nerves the way the current ones do. Such an anesthetic could potentially allow a person, for example, to go to the dentist and eat a pastry afterward, because the mouth muscles would be unaffected, or enable a woman to feel no pain during labor yet still register other sensations in her uterus and retain command of the muscles needed to focus her pushing.

The common local anesthetic lidocaine works by generally depressing the activity of all neurons. But by combining a derivative of lidocaine with capsaicin (the substance that makes chili peppers burn your mouth by binding to the pain receptors that detect burning), Dr. Woolf was able to target the lidocaine derivative into the pain neurons through the channel opened by capsaicin while leaving the other neurons unaffected. His work has been done on rodents, but he has licensed the idea to a pharmaceutical company that is preparing to begin human trials.

Most of Dr. Woolf’s lab’s work of recent years, however, has focused on decoding the genetics of neuropathic pain. “It is clear that pain is a complex disease, involving lots of different genes. We’ve been able to identify several key players,” he said, sounding—in his low-key way—distinctly pleased. “It looks like about 50 percent of variation in neuropathic pain sensitivity is heritable,” he told me.

Some pain research has focused on obscure pain-related genes, looking at interrelated families in Saudi Arabia or Pakistan. Such work has led to the identification of the genetic mutations responsible for the rare, bizarre disease
congenital insensitivity to pain
, which is marked by the inability to feel physical pain. Dr. Woolf’s group has focused instead on the common genes found in different variants throughout the population. He recently identified a gene that produces an enzyme called GCH1 (GTP cyclohydrolase), which is a key modulator of pain sensitivity; one variant of this gene is significantly protective against the development of neuropathic pain.

Can the action of the pain-protective gene variant be copied and introduced as a drug for those who lack it? (Enroll me in that trial!) The gene variant inhibits excessive production of a substance called BH4 (tetrahydrobiopterin), which plays a critical role in pain sensitivity and persistence, with greater amounts of BH4 causing greater sensitivity to pain. Fifteen percent of the population has the lucky gene variant that most strongly limits BH4 production and makes people less susceptible to developing persistent neuropathic pain—and makes healthy humans significantly less sensitive to acute pain in lab experiments.

Dr. Woolf has identified a gene substitute—an agent that inhibits the production of BH4—which he is attempting to develop into a drug. Of course, there can be a long road between discovering a substance that does the job molecularly, so to speak, and turning it into a drug (the substance may be unstable or toxic, or it may dissolve too quickly in the body, or someone else might own the intellectual property!). But the first step has been taken.

Pain Diary:

I Try to Understand Science

BAD NEWS

nociception

pain-sensitivity gene

hyperalgesia, allodynia

central sensitization, peripheral centralization

excitotoxicity, overuse atrophy

cellular pain memory

cortical reorganization

gray matter shrinkage, neuronal loss, atrophy of the circuitry

the pain that pain spawns is ever more malign

GOOD NEWS

developing pain-nerve-specific analgesia

pain-protective gene

agent that mimics pain-protective gene action

hope agent can be turned into drug

the wonderful dream that pain has been taken away from us

IV

FINDING A VOICE:

Pain as Narrative

FINDING A VOICE

Physical pain has no voice, but when it at last finds a voice it begins to tell a story,” Scarry writes, expressing the paradox of the relation between disease and the narrative it inevitably becomes. Pain has no voice. Why, then, does it seem to speak?

When Hippocrates instructed physicians to treat the patient rather than the disease, it was because physicians did not understand disease. Now that science has shown that pain is a biological disease, to treat it otherwise would seem to do the sufferer a disservice: to personalize it, to see it as a state of being (which is what it feels like) rather than a state of the nervous system.

Yet, as lived experience, the disease of pain turns into the individual suffering of illness, an understanding of which requires studying the patient as well as the disease. Recall Foucault’s neat formulation that modern medicine began when the doctor switched from soliciting an illness narrative—“What is the matter with you?”—to asking the medical question “Where does it hurt?” Alas, that insight does not finally or perfectly illuminate pain. For better and for worse, the nature of the person in pain bears on the nature of the pain itself.

What story, then, does pain tell?

INSPIRATION

The pain specialist was half dreading his first consultation in the hospital that morning.
So grim.
The patient was a middle-aged train conductor who suffered from multiple sclerosis. He had fallen from a train one day (MS affects balance) and sustained such severe injuries that his legs and one arm had to be amputated. He was now suffering from the onset of phantom limb pain.

“And he still had MS?” I said without thinking when the doctor later told me the story, as if the universe—having stolen three of the patient’s limbs—would at least recoat the myelin on his aberrant nerve cells.

The doctor recalled how when he walked into the room, the patient was lying in bed reading. “Hey, Doc—have you read this book?” he said, showing him Rachel Naomi Remen’s
Kitchen Table Wisdom
, a book of medical stories. “Some of these people—the things they’ve been through, the way they cope—it’s incredible.”

The doctor did a double take. The patient—
holding the book with his sole remaining limb
—was being inspired by the characters, most of whose medical adversities were less grave than his own. The patient had no idea that his capacity for inspiration would inspire the doctor, such that years later the doctor would tell the story to me and I, too, would feel a quickening (although I had read
Kitchen Table Wisdom
myself and felt only alienated by its stories of ennobling illnesses).

“I always think about that,” the doctor told me. “Why? Why do some people do so well with intractable pain problems while others fall apart with ordinary ones? I’ve had patients with nonspecific lower-back pain give up—go on disability, become depressed, turn into full-time chronic pain patients—while others with more serious conditions are resilient.”

“These lectures—” He made a dismissive motion with his hand about the lecture he and I had just attended about a gene that may or may not play a role in a type of pain.

Is the mystery of resilience a matter of genetics, character, temperament, will, luck? he mused. How can a physician (not a priest, not a magician) help patients who are broken by pain metamorphose into the train conductor whose empathy for the suffering of others is so great he momentarily forgets about his own?

“If we knew the answer to that,” he said, “we would truly know how to heal.”

SUFFERING

Nociception

Pain

Disability

Suffering

Pain Behavior

If pain worked the way it should, these things would reliably follow one another: nociception (the impulses transmitted by nerve cells that detect tissue damage) would cause pain. Pain would cause disability. Disability would cause suffering. Suffering would predictably cause certain pain behavior, so that you could accurately assess how much a person is suffering from the person’s words and actions.

Yet none of this is true. Nociception can cause pain—or not. Certainly, the quality of pain bears no clear relation to the nociceptive input. Pain can cause disability—or not. But the most mystifying relation is that of pain to suffering: there are those who appear to suffer greatly over modest pain and those who appear to suffer far less from great pain. Pain behavior cannot be assumed to provide an accurate guide to the internal experience of suffering. The train conductor, balancing the book of inspirational stories in his one hand, provides a dramatic illustration that extraordinary nociception, pain, and disability do not necessarily occasion extraordinary suffering or pain behavior that demonstrates such suffering.

Sufferers experience their suffering as stemming from something outside them, Dr. Eric J. Cassell writes in
The Nature of Suffering and the Goals of Medicine.
Yet “the factors that convert even severe pain into suffering depend on the particular nature of the individual . . . [T]he pain is the pain that it is and the suffering takes the form it does in part because of the contribution of meanings of the patient. Same disease, different patient—different illness, pain and suffering.”

I had seen this myself in patient after patient. The assignment I had to write about chronic pain should have taken a month or two, if I dallied. I wasn’t being asked to
write a dissertation.
Yet seven months later I was still visiting pain clinics around the country, following the director of each clinic and observing each one’s interactions with patients. Eventually I observed several hundred patients.

After my article was published, in 2001, I decided to write a book because I wanted to answer one crucial thing:
Why do some people get better?
How did the outcomes match the doctors’ original predictions? Was there a recipe for healing, and if so, could I employ it for myself? Why was a West Virginia logger I met, who can no longer work owing to a back injury, suicidal? Yet Holly Wilson—paralyzed from a spinal cord injury—did not seem even mildly depressed. Holly had been paralyzed in a cruelly ironic way: a surgeon accidentally damaged her spinal cord during a minor surgery to remove a bulging disk in her neck.

“I had this neck pain that radiated into my arm,” she explained of her original condition. “I thought it was the worst thing! I complained about it constantly—I couldn’t wait to have the surgery. I had no clue what intractable pain was like.” Now she suffers from the intractable pain, common with spinal cord injuries, that she experiences as coming from her paralyzed body, which she calls her “shadow.” She is loathe to take opioids in the doses required to control her pain. “I like to be clear-headed. Clear-headedness is more important to me than lack of pain.” She tried a spinal cord stimulator, but it made her pain worse. She told me the case settled out of court for a sum that is insufficient to cover a lifetime of medical expenses, and now—ten years later—she fears running out of money.

I kept her hour after hour, interviewing her—watching her face, the way she laughs, the way she holds her head. But behind all my questions I had only one question:
Why haven’t you despaired?
She has pain; she has disability; she describes her pain and disability vividly. Why don’t they seem to cause her greater suffering?

One part of the answer lies in her relationship with her husband. “He’s always there for me,” she said. “I’m sure—I’m 99 percent sure—he’s never going to leave me.” Another part of the answer seems to lie in her relationship with her doctor, Scott Fishman. Although he had not yet been able to adequately control her pain, he was always trying—he always had a plan, six months ahead, of treatments to try. Whenever he heard about experimental treatments, he would find out whether they were suitable for her. “I’ll call anyone in the world about Holly,” he told me. Dr. Fishman’s care for her—and her belief that he was always thinking of her—helped to balm the psychic scar of the fact that the surgeon never personally apologized to her for it or came to visit her in the hospital after the surgery. But Lee Burke had a good relationship with the Nice Doctor—indeed, his empathy blinded her to the failure of his treatment.

“I don’t really know,” said Holly when I asked her directly how she combats despair. “I’m not going to say that I’ve never thought of ending my life because I have and it would be easier for me, but I would never do that to my family. I know I could never do that to my family because my father did.”