Phantom limb pain and causalgia were two clinical pain syndromes that could not be explained in terms of specific nerve pathways. Amputees experienced phantom limbs: the distinct sensation that the missing arm or leg was still attached, often held in a distorted, intensely painful, position. Causalgia, first described by the American physician, Silas Weir Mitchell, was even more puzzling. After an injury had healed, the patient experienced intense, burning pain and sensitivity to the slightest vibration or touch, usually in the hand or foot, but at a site some distance removed from the original wound. Both disorders sometimes persisted for years. Anesthesiologists used localized nerve blocks to relieve the pain and neurosurgeons developed techniques for severing the nerve pathways involved; but neither treatment was consistently successful.

In the great wars, these relatively rare conditions afflicted many soldiers and baffled and disturbed their doctors: Mitchell in the American Civil War, the French surgeon René Leriche in World War I, William Livingston in World War II. How could phantom limb and causalgia be explained in terms of the specific neural pathways that conducted pain sensation directly from the site of tissue damage?

Silas Weir Mitchell (1829-1914)

	Silas Weir Mitchell

In 1872, American neurologist S. Weir Mitchell described a bizarre symptom complex resulting from wounds to peripheral nerves in his book, Injuries of Nerves and Their Consequences: "Perhaps few persons who are not physicians can realize the influence which long-continued and unendurable pain may have on both body and mind. . . Under such torments the temper changes, the most amiable grow irritable, the bravest soldier becomes a coward, and the strongest man is scarcely less nervous than the most hysterical girl. Nothing can better illustrate the extent to which these statements may be true than the cases of burning pain, or, as I prefer to term it, Causalgia, the most terrible of all tortures which a nerve wound may inflict."

Causalgia

Mitchell saw a large number of patients who had been wounded in the Civil War and suffered from a chronic affliction he called causalgia. He wrote: "We have some doubt as to whether this form of pain ever originates at the moment of the wounding. . . Of the special cause which provokes it, we know nothing, except that it has sometimes followed the transfer of pathological changes from a wounded nerve to unwounded nerves, and has then been felt in their distribution, so that we do not need a direct wound to bring it about. The seat of the burning pain is very various; but it never attacks the trunk, rarely the arm or thigh, and not often the forearm or leg. Its favorite site is the foot or hand. . . Its intensity varies from the most trivial burning to a state of torture, which can hardly be credited, but reacts on the whole economy, until the general health is seriously affected....The part itself is not alone subject to an intense burning sensation, but becomes exquisitely hyperanesthetic, so that a touch or tap of the finger increases the pain."

Amputation

	A Civil War Amputee

The common treatment for causalgia associated with peripheral nerve injury was amputation. Mitchell noted the all too common sequelae:

"Sensory hallucination. --- No history of the physiology of stumps would be complete without some account of the sensorial delusions to which persons are subject in connection with their lost limbs. . . Nearly every man who loses a limb carries about with him a constant or inconstant phantom of the missing member, a sensory ghost of that much of himself, and sometimes a most inconvenient presence, faintly felt at time, but ready to be called up to his perception by a blow, a touch, or a change of wind."

Mitchell performed a number of experiments. He wrote: "I recently faradised a case of disarticulated shoulder without warning my patient of the possible result. For two years he had altogether ceased to feel the limb. As the current affected the brachial plexus of nerves, he suddenly cried aloud, 'Oh, the hand, the hand!' The limb is rarely felt as a whole; nearly always the foot or the hand is the part more distinctly recognized. . . In nearly all there is some feeling, such as pain, itching, or other sensation."

René Leriche (1879-1955)

In 1937 Leriche wrote his classic work, Chirurgie de la Douleur (The Surgery of Pain), in which he detailed his work on causalgia and phantom limbs. He acknowledged Mitchell's contribution and looked for ways to solve the problem of pain. As with Mitchell in the Civil War, Leriche's opportunity to study these phenomena came during World War I, when he saw many soldiers with peripheral nerve damage. He observed vasomotor changes which suggested to him an abnormality of vascular stimulation; in 1916, he attempted to alleviate the pain through periarterial sympathectomy.

In 1916 Leriche wrote:

"A few months previously I had unexpectedly encountered one of these cases. I was struck by the resemblance which the condition had to that of a sympathetic disorder: the cyanosis, the sweating, the paroxysmal nature of the pains, the effect on the general mental state, the reference of painful phenomena to a distance--all pointed in that direction. And, remembering that the sympathetic, in its distribution to the limbs, follows the course of the arteries, I asked myself whether, in those case of nerve injury complicated by arterial wounds, it was not the injury to the sheath of the vessel that determined their painful and trophic features--the wound of the sympathetic. . . Starting from this point, I asked myself whether, by acting upon the perivascular sympathetic, I might be able to succeed in modifying the causalgia.

"I saw the patient on the 20th June: the upper limb was completely paralyzed--arm, forearm, hand and fingers. . . dominating everything, was an intense burning pain, concentrated particularly in the palm of the hand and on the pulp of the finger-tips. . . On the 27th August I exposed the brachial artery, which I found small and contracted. I removed its adventitia for a distance of 12 cm. . . By the next day it was obvious that the patient had less pain."

Leriche also saw patients with painful stumps and phantom limb pain. His experience showed clearly that "re-amputation should be avoided. . . and there should be no resection of the neuroma. I have had under my care more than thirty cases of amputation in which neurectomies had been done: none of them had been cured." Leriche found that "novocain infiltrations of the para-vertebral sympathetic chain" provided a new and very effective method for giving relief.

William K. Livingston (1892-1966)

W. K. Livingston had learned at Harvard that pain was a specific response to an unpleasant stimulus, a warning of tissue damage. One of the problems that puzzled him early in his career was visceral pain: patients might experience no apparent pain from tissue damage to certain internal organs but would report "referred pain" in another part of the body. He studied other pain phenomena, such as causalgia and phantom limb pain, which presented similar enigmas. Livingston's research in these areas is described in his books, The Clinical Aspects of Visceral Neurology (1935) and Pain Mechanisms (1943), in which he proposed that pain, far from being a simple reaction to a single stimulus, could involve a complex and diffuse, but interactive, set of neural responses, which Livingston called "the vicious circle."

	Portrait of William K. Livingston, c.1940

Livingston wrote in his Pain Mechanisms (1943): "I believe that the concept of 'specificity' in the narrow sense in which it is sometimes used. . . has led away from a true perspective. . . Pain is a sensory experience that is subjective and individual; it frequently exceeds its protective function and becomes destructive. The impulses which subserve it are not pain, but merely a part of its underlying and alterable physical mechanisms. . . The specificity of function of neuron units cannot be safely transposed into terms of sensory experience.

	Livingston's Case Notes from a WWII Peripheral Nerve Injury Patient

"A chronic irritation of sensory nerves may initiate clinical states that are characterized by pain and a spreading disturbance of function in both somatic and visceral structures. If such disturbances are permitted to continue, profound and perhaps unalterable organic changes may result in the affected part. . . A vicious circle is thus created."

During World War II, Livingston was assigned to the Oakland Naval Hospital, where he assumed responsibility for peripheral nerve injury patients and other difficult pain problems, including causalgia cases which he later described as "every bit as striking as [S. Weir] Mitchell's." He maintained extensive case histories on these patients, including notes, drawings, and follow-up correspondence and kept 1279 of these records, filed by number in three-ring binders, until his death. Livingston used periarterial sympathectomies, ganglion-ectomies, and novocaine blocks to treat his patients, but he recorded several cases where the relief was only temporary and the pain returned.