Silas Weir Mitchell:
Nerve Pain Pioneer

S. Weir Mitchell (1829-1914) earned a reputation as an eminent neurosurgeon during the era of the American Civil War. His 1872 book, Injuries of Nerves and Their Consequences (J.P. Lippencott, Philadelphia), still contains many valid and informative points, including comments on the ability of severe nerve pain to turn the bravest soldier into a trembling coward. In 1872, 34 years before Dejerine and Roussy published their landmark study on central pain, Mitchell made the following observations on nerve injury pain.

• In contrast to ordinary pain, which tends to be worse in the evening, the person with nerve injury pain awakes with it and it "pursues him with increasing torture throughout the day" Weir was contrasting it with toothache pain, which doesn't get going until there has been time for circulation to occur during the day.
• The "remote" cause of nerve injury pain is in the wound, while the "immediate" cause is in the site of origin of the nerve; a very astute observation and ahead of Dr. Mitchell's time. Spontaneous and evoked pain would be consistent with this theoretical arrangement wherein immediate causation results in spontaneous continuous pain while stimulation of an area of the body elicits greater pain as the "remote" augmenting location.
• In most gunshot wounds when chronic nerve injury pain appears, it is usually a burning pain, while at the time of direct physical injury to a nerve, other forms of pain are to be found. Discussing this, Mitchell gave his famous quote, "Under such torments the temper changes, the most amiable grow irritable, the soldier becomes a coward, and the strongest man is scarcely less nervous than the most hysterical girl" (Injuries of Nerves, p 196)
• The burning almost always arises during the healing of the wound and is described as burning, mustard red hot, or like a red hot file rasping the skin". (typical, garden variety, description for what today is called "dysesthesia")
• The most pronounced site of the burning pain is "the hand and foot" (this is the distal gradient also described by Roussy), where the dysesthesia is most severe on the palm of the hand and the top of the foot. The compromise in sensation is greatest where the causalgia, or burning pain, is greatest (This pattern is consistent with that related by central pain patients today).
• Cold weather usually eased the pain while heat made it worse. (This again is typical of Central Pain to a point, since it is really changes in temperature which begin the sensitization-its completion can occur at either temperature extreme. In ciguatera poisoning, the change of cold to a hot burning has been called "cold reversal".
• The burning is not a referred sensation since division of nerves going to the area did not stop the pain. (Once again, Mitchell astutely realized that it was not the nerves themselves causing the pain but something else. Today we would point to the fact Central Pain comes from the brain due to chemical impact of altered genes in the spinal cord neurons, and that evocation occurs with input from kinins, prostonoids, and the similar sensitizing chemicals near the area of applied stimulus.)
• The pain from injury to peripheral nerves occurs immediately when the skin is touched while evoked nerve pain injury in the central nervous system (Central Pain) is delayed from the time of the touch. (We speak of "temporal summation" of dysesthesia today--Mitchell cites measurements by Cruvalhier with a watch indicating quarter seconds). This very important feature of Central Pain, the delay from stimulus until onset of evoked dysesthesia is the major distinguishing characteristic of Central neuropathic pain from Peripheral Neuropathic pain and a an extremely useful clinical test for differentiation of central versus peripheral neuropathy. This should quite possibly be called "Mitchell's Sign", since he was the first to describe it. (Injuries of Nerves p.225)
• A contusion (bruise) is more likely to give rise to more serious injury than direct mechanical injury to the nerve, with "bruised" nerves more likely to pass into chronic pain than a direct wounding of the nerve (i.e. Central pain is an intermediate injury and requires some level of functioning for it to be generated).
• Injured nerves sometimes displayed centrally progressive deterioration. (This brings to mind the modern phrase from Patrick Wall, "Peripheral injury induces central change.")
• Injured nerves sometimes give rise to fibrillar spasms and cramps occur for no particular reason. Weir Mitchell found this reminiscent of the phenomenon in healthy nerves wherein nerves which have been cooled by icing, when tapped, send muscles into sudden spasm. (Recent fMRI studies have shown the cerebellum tends to keep muscles on alert, possibly an abnormal variety of "being on alert" for escape from pain).
  
• It is not possible to explain why an identical injury will sometimes reach the cerebrum and sometimes not.

S. Weir Mitchell was a third generation physician and was as a boy spent many hours fascinated by his father's experiments. When he was just 15 he was admitted to the University of Pennsylvania in his hometown of Philadephia. He was forced to withdraw just two years later due to his father's poor health and the necessity, in his role as the eldest of seven children, of supporting his family. However in 1848, when his father recuperated, he entered Jefferson Medical College for a two-year course of study.

Upon completing medical school, Mitchell traveled and studied in Europe for about a year, then returned to Philadelphia to train under his father and work with poor patients at the Southwark Dispensary. In 1862, during the American Civil War, he resisted pressure to become a brigade surgeon and elected to retain his civilian status and become a contract surgeon in the veterans' hospitals of Philadelphia. His work at the hospitals was very trying and at the close of the Civil War he left his service with the Union Army and spent two months traveling in England and France.

Mitchell was known not only for his brilliance in the medical field, but also for his literary creativity, both poetry and novels. While his writing was noted for its drama, romance, and humor. But, of course, his medical knowledge was revealed as well. One of his best remembered works is "The Case of George Dedlow." This story, published anonymously in the Atlantic Monthly in 1866, tells the story of a young man who, as a result of war injuries, had his arms and legs amputated, leaving just his torso. This is the first known written account of phantom limb pain, and it accurately describes the hallmark symptoms of nerve injury pain, such as dysesthetic burning. In another work, a poem titled, " The Shriving of Guinivere," he expressed his compassion and understanding of the suffering he witnessed:

When as she trembling rose again,
And felt no more in heart and brain
The weary weight of sin and pain,
For him that healed she looked in vain

Mitchell was also known for his humor and his vanity. Both of these traits are demonstrated by the account of a visit he paid to the famous French phyiscian Charcot, who later trained Freud as a medical doctor. When Mitchell arrived, rather than ask the secretary to announce his arrival, he provided the secretary with a list of imaginary symptoms for a supposed new patient and instructed the secretary to tell Charcot that the patient was soon leaving for America. When she related the "symptoms" to Charcot he told her that he recommended the patient postpone treatment until he could be seen by Mitchell in America!

Mitchell continued his medical practice and his writing until just a couple of weeks before his death in 1914 from influenza. Thankfully he has left us with the legacy of his medical wisdom and his literary talent.