In Memoriam

Patrick D. Wall, DM, FRS
1925-2001

A Remembrance

On August 8, 2001, the field of pain research lost its major figure and dominant personality: Patrick D. Wall. His discoveries were seminal, his ideas revolutionary, and his influence pervasive and ongoing. Scientists are particularly indebted to him, including those who were energized by his lively criticism and provocative ideas. His discoveries and his interpretations permeate much of what we currently believe about the pain sensory system. In addition to his scientific impact, he, along with John Bonica, was a critical figure in the early growth of the field of pain treatment. He was the founding editor of the journal Pain and later co-editor with Melzack of the Textbook of Pain, which has gone into its fourth edition. He wrote or co-authored several books on the subject for the lay public. His dedication to understanding and improving the treatment of those suffering from pain has created a legacy of compassion and caring.

He is best known for his classic theoretical paper with Ron Melzack in Science in 1965, "Pain mechanisms: a new theory," which proposed the famous gate control hypothesis. Less broadly appreciated outside the research community is that he was a prolific, innovative, and rigorous electrophysiologist, with close to 300 publications on a variety of subjects related to pain. In the 1950s and 1960s he interacted with leading neurophysiologists at the University of Chicago, Yale, and MIT. At that time, the pioneering work of Jerry Lettvin, Stephen Kuffler, and Vernon Mountcastle had shown through single-unit recording that neurons in central sensory pathways functioned as feature detectors. Wall immediately grasped the significance of this approach and, with his colleagues and students, discovered characteristic somatosensory features to which several classes of dorsal horn neuron are tuned. These include low-threshold mechanoreceptors and nociceptive wide-dynamic-range neurons. This approach led to his pioneering work on the physiological lamination of the dorsal horn. These discoveries not only laid the foundation for the core of our current understanding of pain processing in the spinal cord, they served as a catalyst for the explosive growth of the field of pain research in subsequent years. People are continuing to build on these discoveries of a half-century ago.

Wall and his colleagues were the first to record from identified spinothalamic tract neurons and from the small neurons in the substantia gelatinosa. With Michael J. Gutnick, Wall was the first to show that damaged primary afferents develop spontaneous activity and, with several other colleagues, that peripheral nerve injury leads to reorganization of connections in the dorsal horn. Wall was also the first to appreciate the modulatory significance of presynaptic inhibition in the dorsal horn. His work suggested that substantia gelatinosa neurons presynaptically control the central terminals of primary afferent nociceptors. In fact, a subset of substantia gelatinosa neurons (enkephalinergic) most likely does presynaptically control nociceptor terminals. The important point is that over the five decades of his scientific career, Wall was consistently ahead of the field with experiments that were technically challenging, results that were reproducible, and ideas that were innovative and seminal. His great stature in the field was earned through hard work, scholarship, and creativity. He never lost sight of the big picture, never ignored the troubling paradoxes that vexed other scientists and clinicians. He never stopped reminding us of such questions as: How can there be pain with no tissue injury? How can there be tissue injury with no pain?

However, to describe his work and ideas does not do justice to, nor does it fully explain his impact on the field and upon those who were fortunate enough to interact with him personally. He had a charismatic personality which, along with his published work, contributed greatly to his leadership. The irrepressible twinkle in his eye and the smile on his face made it clear that he enjoyed his work and his interactions with colleagues. These qualities were honed by his social interactions, often over a drink at a local pub. The continual rolling and smoking of cigarettes magnified his intensity. He was intense, yet playful and gregarious.

Conflict and debate were his stock–in-trade. He skillfully used controversy to draw attention to his ideas. While his hypotheses were consistently heuristic, my impression is that it was of equal importance to him that they be interesting, provocative, and, best of all, iconoclastic. For him, every experimental result had to have a story to go with it, preferably strange, off-beat, and counter-intuitive. If there was an odd slant to an interpretation or an idea, that held a special fascination for him. Like an avant garde playwright, he seemed to enjoy nothing better than to disturb people by openly challenging their most cherished ideas. For those who could handle this confrontational approach, the experience was often exhilarating.

One of his strategies was to roundly (and caustically) criticize another scientist’s views and to question the validity or significance of some widely accepted idea. His resistance to accepting the existence (and later, the importance) of nociceptive specific primary afferents and dorsal horn neurons at times seemed Quixotic. Once while he was arguing this point I asked him if he really believed that unmyelinated polymodal nociceptors did not contribute to pain sensation. He answered, "Of course not, but wouldn’t it be interesting if it were true?" This is precisely the sort of mental playfulness that is the substance of creativity. Over time I began to appreciate the method behind his iconoclasm: If you don’t call the dogma into question, you will never change it. He was continually challenging the field to deal with its paradoxes and inconsistencies.

I last saw Pat in London at the International Headache Society meeting, September 6, 2000. He was subdued and just detectably slowed. Due to his chemotherapy his walking had become difficult, particularly negotiating stairs. However, in other ways, at 75 he had changed surprisingly little. He was slightly bald and his midlength, bushy, reddish-brown beard was speckled with white. His blue eyes were wide open, alert, inquisitive, and sparkling in an easy smile. I noticed for the first time that his hands were smallish, delicate, and almost feminine, in sharp contrast with his very masculine face and powerful, resonant voice. He gave an excellent and highly original lecture proposing that migraine represents one side of a bistable flip-flop system. As usual, his talk was articulate, analytical, and self-assured. His speaking style was animated and engrossing. His voice had the music of confidence and of a person with something novel and interesting to say. The tone and pace of his presentation added to the interest and lucidity of his argument. Without any visual aids he was able to paint his ideas clearly. His sense of organization and timing were impeccable, his scholarship impressive. He began his talk with the phrase, "Let us take a step back." Of course, this is the essence of creative scholarship. I highly recommend it to all.

Howard L. Fields, MD, PhD