Harvard Medicine

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The Pain of Our Existence

The instinct to respond to potential danger helps keep us alive.

How the body feels sensations—a brush of fingertips or the heat from a nearby iron—is a complicated business. Why it feels, however, is simple: Our survival depends on it.

Not only do we need to know what might harm us, we must also remember how to respond to dangers. Fortunately, biology has provided us with the perfect protection mechanism. It is called pain.

“Pain is such a fundamental sensation,” says Anne Louise Oaklander, an HMS associate professor of neurology and director of the Nerve Injury Unit at Massachusetts General Hospital, “that rare individuals born without pain sensation often die in childhood.”

“Pain signals also are tied into learning and memory,” she adds. “We might forget the name of our fourth-grade teacher, but nobody forgets that a flame burns.”

Thus acute pain, the short, perhaps excruciating, reaction to an environmental cue, helps keep us alive and away from harm. Pain becomes a problem, however, when its useful unpleasantness becomes unending.

Acute pain might cause us to yelp, recoil, or exhibit other help-eliciting behaviors, but in chronic pain, these behaviors extinguish. Yet the pain itself—unrelenting tensed muscles or burning sensations, for example—remains distressingly insistent although unapparent to others.

Unraveling the neurologic basis for chronic pain drives the investigations of many neuroscientists, including Oaklander. Her research has yielded insights into its causes and cleared some paths toward its better diagnosis and treatment.

One area in which Oaklander and others have provided clarity is our understanding of the characteristics and operations of pain-registering nerve cells in the skin called nociceptors. When damaged by direct inflammation or other insult, these sensitive sentinels can misfire, bombarding the brain with unfocused messages. Nociceptor degeneration from injury or illness also can miscue the spinal cord and brain to signal pain after such nonpainful stimulation as light touch—or even without any sensory stimulation. This inappropriate signaling by central pain neurons deprived of normal input from periphery neurons, what Oaklander calls “phantom-skin pain,” is akin to the excessive firing of the brain’s pain neurons when the body loses limbs or other parts.

Proper diagnosis is critical to stemming this cascade of effects. Yet nociceptors are the merest of threads: They do not even register in standard nerve-damage tests such as reflex checks of the knees or electromyography and nerve conduction studies. So Oaklander uses a skin-biopsy technique that uses immunolabeling to highlight the endings of viable nociceptors, allowing researchers to determine their densities. Low densities indicate nerve damage as the cause of chronic pain.

Oaklander expects future studies to lead to new diagnostic tools, identification of new pain diseases, and better understanding of nociceptors and their role in chronic pain.

“Neuropathic pain is still in the mid-twentieth century,” says Oaklander. “It’s the Wild West of medicine.”



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