Neuropathic Pain

Neuropathic Pain

There are a whole host of haunting pains that torment us for reasons we do not understand and that arrive from we know not where – pains without return address. Lord Nelson, the British admiral, los his right arm in an attack on Santa Cruz de Tenerife in 1797. Soon afterward, Ramachandran points out, he vividly began to experience the presence of his arm, a phantom limb that he could feel but not see. Nelson concluded that its presence was “direct evidence for the existence of the soul,” reasoning that if an arm can existe after being removed so then might the whole person exist after the annihilation of the body.

Phantom limbs are troubling because they give rise to a chronic “phantom pain” in 95 percent of amputees that often persists for a lifetime. But how do you remove a pain in an organ that isn't there?

Phantom pains torment soldiers with amputations and people who lose limbs in accidents, but they are also part of a larger class of uncanny pains that have confused doctors for millennia, because they had no known source in the body. Even after routine surgery, some people are left with equally mysterious postoperative pains that last a lifetime. The scientific literature on pain includes stories of women who suffer menstrual cramps and labor pains even after their uteruses have been removed, of men who still feel ulcer pain after the ulcer and its nerve have been cut out, and of people who are left with chronic rectal and hemorrhoidal pain after their rectums were removed. There are stories of people whose bladders were removed who still have an urgent, painful chronic need to urinate. These episodes are comprehensible if we remember that they too are phantom pains, the result of internal organs being “amputated”.

Normal pain, “acute pain,” alerts us to injury or disease by sending a signal to the brain, saying, “This is where you are hurt – attend to it.” But sometimes an injury can damage both our bodily tissues and the nerves in our pain systems, resulting in “neuropathic pain,” for which there is no external cause. Our pain maps get damaged and fire incessant false alarms, making us believe the problem is in our body when it is in our brain. Long after the body has healed, the pain system is still firing and the acute pain has developed an afterlife.

The phantom limb was first proposed by Silas Weir Mitchell, an American physician who tended the wounded at Gettysburg and became intrigued by an epidemic of phantoms. 

Physicians have long known that a patient who expects to get pain relief from a pill often does, even though it is a placebo containing no medication. Illustration by Megan Jorgensen.

Civil War soldiers' wounded arms and legs often turned gangrenous, and in an age before antibiotics, the only way to save the soldier's life was to amputate the limb before the gangrene spread. Soon amputees began to report that their limbs had returned to haunt them. Mitchell first called these experiences “sensory ghosts,” then switched to calling them “phantom limbs.”

They are often very lively entities. Patients who have lost arms can sometimes feel them gesticulating when they talk, waving hello to friends, or reaching spontaneously for a ringing phone.

A few doctors thought the phantom was the product of wishful thinking – a denial of the painful loss of a limb. But most assumed that the nerve endings on the stump end of the lost limb were being stimulated or irritated by movement. Some doctors tried to deal with phantoms by serial amputations, cutting back the limbs – and nerves – farther and father, hoping the phantom might disappear. But after each surgery it reemerged.

Ramachandran had been curious about phantoms since medial school. Then in 1991 he read the paper by Tim Pons and Edward Taub about the final operations on the Silver Spring monkeys. Pons mapped the brains of the monkeys who had had all the sensory input from their arms to their brains eliminated bu deafferentation and found that the brain map for the arm, instead of wasting away, had become active and now processed input from the face – which might be expected because, as Wilder Penfield has shown, the hand and facial maps are side by side.

Ramachandran immediately thought that plasticity might explain phantom limbs because Taub's monkeys and patients with phantom arms were similar. The brain maps for both the monkeys and the patients had been deprived of stimuli from their limbs. Was it possible that the face maps of amputees had invaded the maps for their missing arms, so that when the amputee was touched on the face, he felt his phantom arm? And where, Ramachandran wondered, did Taub's monkeys feel it when their faces were stroked – on their faces, or in their “deafferented” arm?

Pain, like the body image, is created by the brain and projected onto the body. This assertion is contrary to common sense and the traditional neurological view of pain that says that when we are hurt, our pain receptors send a one-way signal to the brain's pain center and that the intensity of pain perceived is proportional to the seriousness of the injury. We assume that pain always files an accurate damage report. This traditional view dates back to the philosopher Descartes, who saw the brain as a passive recipient of pain. But that view was overturned in 1965, when neuroscientists Ronald Melzack (a Canadian who studied phantom limbs and pain) and Patrick Wall (an Englishman who studied pain and plasticity) wrote the most important article in the history of pain. Wall and Melzack's theory asserted that the pain system is spread throughout the brain and spinal cord, and far from being a passive recipient of pain, the brain always controls the pain signals we feel. 

Their “gate control theory of pain” proposed a series of controls, or “gates”, between the site of injury and brain. When pain messages are sent from damaged tissue through the nervous system, they pass through several “gates”, starting in the spinal cord, before they get to the brain. But these messages travel only if the brain gives them “permission,” after determining they are important enough to be let through. If permission is granted, a gate will open and increase the feeling of pain by allowing certain neurons to turn on and transmit their signals. The brain can also close a gate and block the pain signal by releasing endorphins, the narcotics made by the body to quell pain. How much pain we feel is determined in significant part by our brains and minds – our current mood, our past experiences of pain, our psychology, and how serious we think our injury is.

When a mother soothes her hurt child, by stroking and talking sweetly to her, she is helping the child's brain turn down the volume on its pain. Illustration by Megan Jorgensen.