- Email: [email protected]
Histocal Profile: Patrick D. Wall, DM, FRCP, FRS
BULLETIN
B. Berthold Wolff
and New York University’s Tisch Hospital (since 1960) research professorship in psychology at NYU School of Medicine (since 1976) research professorship of behavioral sciences and community health at NYU College of Dentistry (since 1976) and directorship of the NYU Comprehensive Pain Center (since 1977). Among Wolff’s many areas of professional interest and expertise have been the behavioral mechanisms of pain, acute and chronic pain management, pain measurement, ethical problems in research, and pain center administration. In addition to his pivotal role in APS, Wolff holds numerous memberships in professional and scientific associations, and he has held leadership positions with several, including president of the Arthritis Foundation (1968-1970) and founder and president of the Eastern Pain Association (1976-1978). He has authored and coauthored many articles on the study of pain.
H
Patrick Wall and the study of pain have been synonymous for the past 25 years. His contributions to the field have been widely recognized and rewarded, not least as the first recipient of the Bristol-Myers Squibb Award for excellence in pain research, but also by his election as a fellow of the Royal Society. In his pursuit of scientific excellence, in his single-minded obsession with originality and innovation, he has constantly-and in many cases seemingly deliberately- courted controversy. This has made him afascinating, eccentric, and larger-than-life individual, admired by many, loathed by a few, but ignored by nobody. The razor-sharpness of his tongue, his wit, and his charm are as distinctive a set of features as his utter dedication to experimental investigation of pain mechanisms. Wall is nowhere as happy as rolling a cigarette beside the lathe adapted from his MIT days as an electrophysiology set-up. From this setup, encrusted with the effort of decades-and a possibly less-than-fastidious attitude to laboratory hygiene-have emerged some of the most important data and ideas about how pain is generated. Wall was born in Nottingham, England, and educated at St. Paul’s, Oxford, and the Middlesex Hospital Medical School, from which he received his medical degree soon after the end of World War II. In 1948, he crossed the Atlantic, variously stopping at Yale, the University of Chicago, and Harvard Medical School, until in 1957 he set up shop at MIT for 10 years. From the early work with Lettvin, McCulloch, and Pitts emerged the first strands of his work on transmission in the spinal cord and the interaction between excitatory and inhibiting influences on sensory processing.’ His major early contributions were in the study of presynaptic inhibition, investigated
istorical Profile: Patrick D. Wall, DM, FRCP, FRS Clifford
J. Woolf
Editor’s note: As noted in the last issue, APS Journal plans to publish biographies of each winner of the Bristol-Myers Squibb Award for Distinguished Achievement in Pain Research. In 1988, Patrick D. Wall became the first recipient of this award. Clifford Woolf, MBBCh, PhD, MRCP, a colleague of Wall’s at University College London, contributed this biography.
299
Patrick D. Wall
300
BULLETIN
by the excitability changes produced during primary and the first recording of afferent depolarization,22 receptive field responses from dorsal horn neurons.23 Both gave rise to a torrent of work that is continuing. In the early 196Os, Wall began a collaboration with Canadian psychologist Ronald Melzack14 that reached an explosive pitch with the development of the spinal gate control theory.15 The impact of this work on neurobiologists and clinicians was immense and has changed forever the way in which we think about the sensation of pain. Wall’s logo, the model of Descartes, has been introduced at hundreds of lectures, to be knocked off its pedestal by his lucid arguments, to the fury of some thoroughgoing specificitists. The spinal gate control theory encapsulated work on the responses of neurons to particular types of afferent input17 and led directly to a novel form of pain therapy-transcutaneous electrical nerve stimulation4’ During the second half of the 1960% Wall continued analyzing the functional and structural organization of the spinal cord, examining its laminar patterns of connectivity and descending influences,24 activity in freely moving animals, 33 the response to visceral inputs2’ primary afferent terminations5 and the factors controlling receptive fields6 He also returned to England, invited by J. 2. Young to the Department of Anatomy and Embryology at University College London. There his work took on new directions, exploring the effect of deafferentation2g and introducing the concept of ineffective synapses,18 and in a dramatic flourish of papers, he began to study experimental nerve injury, the first serious investigation of neuropathic pain.34,42 Through his fascination with long-ranging afferent fibers in the spinal cord,43 he began to investigate the active responses of central neurons to dorsal root’11g*25 and peripheral nerve injury,2 leading to an investigation of the properties of cells in substantia gelatinosa37 and neuromas.26,3g A major aspect of his current work has returned to these long-ranging afferents. His work on peripheral nerve injury was based both in London and Jerusalem, where since 1972 he has been a visiting professor at the Hebrew University in Jerusalem and where his extremely productive and ongoing collaboration with Marshall Devor flowered.3s4*27 For such a strong individualist, Wall’s scientific work has been characterized by amazingly successful collaborations: with Melzack, continuing today with the jointly edited Textbook of Pain,36 with William Noordenbos,20~3g with Maria Fitzgerald,30-32,38
and with Stephen McMahon,*-I3 among others. I consider myself extremely privileged to be one of those.44-46 Apart from his work on acute and chronic pain mechanisms, Wall has played a major role in establishing pain as a serious scientific discipline through his editorship of the journal Pain. He also has brought the field to a wider audience through hisvery successful book, The Challenge of Pain, written with Melzack.” Most recently, he has co-written a book with Mervyn Jones for pain sufferers.35 Entitled Defeating Pain, it explains simply and directly the nature of the problem, to the understanding of which he has dedicated his career. In this article, I have selected only a tiny portion of Wall’s prodigious and ongoing work. Choosing a few works from so much material of quality and importance has turned out to be arbitrary, especially when one considers that Wall’s total output is close to 300 pieces and includes a paper published in Nature in 1947 on a rotating knife that causes brain lesions, a novel entitled Trio published in 1966, and many pithy and pertinent editorials including one in Pain that introduced the concept of preemptive analgesia.26 I hope this brief summary conveys some flavor of the man-sometimes irascible, often excessive, but always exceptional. Clifford Woolf is professor of neurobiology in the department of ana tomy and developmental biology, University College London.
References 1. Basbaum Al, Wall PD: Chronic changes in the response of cells in adult cat dorsal horn following partial deafferentation: the appearance of responding cells in a previously non-responsive region. Brain Res 116:181-204, 1976 2. Devor M, Wall PD: Reorganization of spinal cord sensory map after peripheral nerve injury. Nature 275: 75-76, 1978 3. Devor M, Wall PD: The effect of peripheral nerve injury on receptive fields of cells in the cat spinal cord. J Comp Neurol 199:277-291, 1981 4. Devor M, Wall PD: Plasticity in the spinal cord sensory map following peripheral nerve injury in rats. J Neurosci 1:679-684, 1981 5. Heimer L, Wall PD: The dorsal root distribution of the substantial gelatinosa of the rat with a note on the distribution in the cat. Exp Brain Res 6:89-99, 1968 6. Hillman P, Wall PD: Inhibitory and excitatory factors controlling lamina 5 cells. Exp Brain Res 9:284-306, 1969 7. Lettvin JY, Wall PD, Howland B, et al: Inhibition of impulses travelling in the primary afferent dorsal column fibres of cat spinal cord. Fed Proc 13:87, 1954
BULLETIN
8. McMahon SB, Wall PD: A system of rat spinal cord lamina 1 cells projecting through the contralateral dorsolateral funiculus. J Comp Neurol 214:217-223, 1983 9. McMahon SB, Wall PD: Receptive fields of rat lamina 1 projection cells move to incorporate a nearby region of injury. Pain 19:235-247, 1984 10. McMahon SB, Wall PD: The distribution and central termination of single cutaneous and muscle unmyelinated fibres in rat spinal cord. Brain Res 359:39-48, 1985 11. McMahon SB, Wall PD: Physiological evidence of branching of peripheral unmyelinated sensory afferents. J Comp Neurol261:130-136, 1987 12. McMahon SB, Wall PD: Descending excitation and inhibition of spinal cord lamina 1 projection neurones. J Neurophysiol59:1204-1219, 1988 13. McMahon SB, Wall PD: Changes in spinal cord reflexes after cross anastomosis of cutaneous and muscle nerves in the adult rat. Nature 342:272-274, 1989 14. Melzack R, Wall PD: On the nature of cutaneous sensory mechanisms. Brain 85:331-356, 1962 15. Melzack R, Wall PD: Pain mechanisms: a new theory. Science 150:971-979, 1965 18. Melzack R, Wall PD: The challenge of pain. Penguin Education, London, 1982 17. Mendell LM, Wall PD: Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres. Nature 206:97-99, 1965 18. Merrill EG, Wall PD: Factors forming the edge of a receptive field: the presence of relatively ineffective terminals. J Physiol 226:825-846, 1972 19. Millar J, Basbaum Al, Wall PD: Restructuring of the somatotopic map and appearance of abnormal neuronal activity in the gracile nucleus after partial deafferentation. Exp Neurol 50:659-672, 1976 20. Noordenbos W, Wall PD: Implications of the failure of nerve resection and graft to cure chronic pain produced by nerve lesions. J Neurol Neurosurg Psychiatr 44:1068-1073, 1981 21. Pomeranz B, Wall PD, Weber WV: Cord cells responding to fine myelinated afferents from visceral muscle and skin. J Physiol 199:51 l-532, 1968 22. Wall PD: Excitability changes in afferent fibre terminations and their relation to slow potentials. J Physiol 142:1-21, 1958 23. Wall PD: Cord cells responding to touch damage and temperature of skin. J Neurophysiol 23:197-210, 1960 24. Wall PD: The laminar organization of dorsal horn and effects of descending impulses. J Physiol 188: 403-423, 1967 25. Wall PD: The presence of ineffective synapses and the circumstances which unmask them. Phil Trans Roy Sot Lond B 278:361-372, 1977 26. Wall PD: The prevention of postoperative pain (editorial). Pain 33:289-290, 1988 27. Wall PD, Devor M: The effect on peripheral nerve injury on dorsal root potentials and on transmission of affer-
28. 29. 30. 31.
32.
33. 34. 35. 36. 37. 38.
39. 40. 41. 42. 43.
44.
45.
301
ent signals into the spinal cord. Brain Res 209:95-l 11, 1981 Wall PD, Devor M, lnbal R, et al: Autotomy following peripheral nerve lesions; experimental anaesthesia dolorosa. Pain 7:103-113, 1979 Wall PD, Egger MD: Formation of new connections in adult rat brains after partial deafferentation. Nature 232:542-545, 1971 Wall PD, Fitzgerald M: Effects of capsaicin applied locally to adult peripheral nerve. I. Physiology of peripheral nerve and spinal cord. Pain 11:277-363, 1981 Wall PD, Fitzgerald M: If substance P fails to fulfill the criteria as a neurotransmitter in somato-sensory afferents, what might be its function? In “Substance P in the nervous system,” CIBA Foundation Symposium 91, Pitman, London, 1982 Wall PD, Fitzgerald M, Nussbaumer JV, et al: Somatotopic maps are disorganised in adult rodents treated with capsaicin as neonates. Nature 295:891-693, 1982 Wall PD, Freeman J, Major D: Dorsal horn cells in spinal and in freely moving rats. Exp Neurol 19: 519-529, 1967 Wall PD, Gutnick M: Properties of afferent nerve impulses originating from a neuroma. Nature 248:740-743, 1974 Wall PD, Jones M: Defeating pain: the war against a silent epidemic. Plenum, New York, 1991 Wall PD, Melzack R (eds): Textbook of pain. 2nd ed. Churchill Livingstone, New York, 1989 Wall PD, Merrill EG, Yaksh TL: Responses of single units in laminae 2 and 3 of cat spinal cord. Brain Res 160:245-260, 1979 Wall PD, Mills R, Fitzgerald M, Gibson SJ: Chronic blockade of sciatic nerve transmission by tetrodotoxin does not produce central changes in the dorsal horn of the spinal cord of the rat. Neurosci Lett 30:315-320, 1982 Wall PD, Noordenbos W: Sensory functions which remain in man after complete transection of dorsal horns. Brain 100:641-653, 1978 Wall PD, Scadding JW, Tomkiewicz MM: The production and prevention of experimental anaesthesia dolorosa. Pain 6:175-182, 1979 Wall PD, Sweet WH: Temporary abolition of pain in man. Science 155:108-109, 1967 Wall PD, Waxman S, Basbaum Al: Ongoing activity in peripheral nerves: III. Injury discharge. Exp Neurol45: 576-589, 1974 Wall PD, Werman R: The physiology and anatomy of long ranging afferent fibres within the spinal cord. J Physiol (Lond) 255:321-334, 1976 Wall PD, Woolf CJ: Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol 356: 443-458, 1984 Woolf CJ, Wall PD: Chronic peripheral nerve section diminishes the primary afferent A-fibre mediated inhi-
302
BULLETIN
bition 77-85, 46. Woolf mary longed rosci
P
of rat dorsal horn neurones. Brain Res 242: 1982 CJ, Wall PD: The relative effectiveness of C-priafferents of different origins in evoking a profacilitation on the flexor reflex in the rat. J Neu6:1433-1442, 1986
ain History Musings William
D. Willis, Jr.
note: APS Bulletin has invited all the past presidents of the American Pain Society to share their views on the practice of pain management-past, present, and future. This issue features the reflections of William 0. Willis Jr., MD, PhD, the fourth president of APS, whose term ran from 7982 to 1983. Willis is Ashbel Smith Professor and Chairman, Department of Anatomy and Neurosciences, and Director of the Marine Biomedical Institute, University of Texas Medical Branch at Galveston. Editor’s
My Back Door Entry into the Field of Pain Research Although pain was one of the many nervous system topics that interested me as a medical student when I graduated from the University of Texas Southwestern Medical School in Dallas in 1960, the field I entered during my PhD training at the Australian National University in Canberra, Australia, in the laboratory of Sir John C. Eccles, MD, was the neuro-
William
D. Willis,
Jr.
physiology of motor control at the spinal cord level. Few, if any, basic science laboratories in the world at that time could be described as engaged primarily in pain research, but many were concerned with motor control. Most of the collaborative experiments with Eccles and Robert F. Schmidt, DrMed, PhD, were on presynaptic inhibition and included a study on the role of GABA. An important lesson was how to identify motoneurons innervating different muscles by antidromic activation. This method of identification also was applied in experiments on neurons that project in the dorsal and ventral spinocerebellar tracts. Although I was not involved in any published work on Renshaw cells or other types of interneurons, I did take note of the difficulties in studying interneurons. In a postdoctoral year at the physiology institute of Giuseppi Moruzzi, MD, in Pisa, Italy, my research background was broadened to include the neurophysiology of the brainstem reticular formation. Moruzzi’s group was working on the role of the reticular formation in arousal and the sleep-wake cycle, and France Magni, MD, and I examined the inputs from the cerebral cortex and spinal cord to antidromically identified reticulospinal neurons, using intracellular recording. Following my formal training period, I returned to Dallas as a faculty member in the department of anatomy. My first National Institutes of Health (NIH) grant was on the organization of muscle afferent connections to motoneurons of the cervical spinal cord, a topic that Robert Schmidt and I had begun to study in Canberra. While in Dallas, I interacted frequently with Parkhurst Shore, PhD, and Andres Goth, MD, in the department of pharmacology, and this stimulated an interest in the pharmacology of monoamines. Challenged by the suggestion of Madge and Arnold Scheibel’s that Renshaw cells don’t really exist, I did a collaborative study with my wife, Jean C. Willis, in which we made a primitive effort to mark the location of Renshaw cells and found that they were in lamina VII, rather than in lamina VIII, as the Scheibels had assumed. We contrasted the response properties of Renshaw cells with those of neurons located in lamina VIII and found that some of the latter projected rostrally toward the brain. This led to the idea of studying ascending tract cells in the ventral horn, and I decided to start with spinothalamic tract (STT) cells activated antidromically from the lateral thalamus. It turned out that STT cells in the cat lumbar spinal cord are concentrated in laminae VII and VIII. The reason for picking tract cells rather than interneurons was the difficulty in defining the role of
B. Berthold Wolff
and New York University’s Tisch Hospital (since 1960) research professorship in psychology at NYU School of Medicine (since 1976) research professorship of behavioral sciences and community health at NYU College of Dentistry (since 1976) and directorship of the NYU Comprehensive Pain Center (since 1977). Among Wolff’s many areas of professional interest and expertise have been the behavioral mechanisms of pain, acute and chronic pain management, pain measurement, ethical problems in research, and pain center administration. In addition to his pivotal role in APS, Wolff holds numerous memberships in professional and scientific associations, and he has held leadership positions with several, including president of the Arthritis Foundation (1968-1970) and founder and president of the Eastern Pain Association (1976-1978). He has authored and coauthored many articles on the study of pain.
H
Patrick Wall and the study of pain have been synonymous for the past 25 years. His contributions to the field have been widely recognized and rewarded, not least as the first recipient of the Bristol-Myers Squibb Award for excellence in pain research, but also by his election as a fellow of the Royal Society. In his pursuit of scientific excellence, in his single-minded obsession with originality and innovation, he has constantly-and in many cases seemingly deliberately- courted controversy. This has made him afascinating, eccentric, and larger-than-life individual, admired by many, loathed by a few, but ignored by nobody. The razor-sharpness of his tongue, his wit, and his charm are as distinctive a set of features as his utter dedication to experimental investigation of pain mechanisms. Wall is nowhere as happy as rolling a cigarette beside the lathe adapted from his MIT days as an electrophysiology set-up. From this setup, encrusted with the effort of decades-and a possibly less-than-fastidious attitude to laboratory hygiene-have emerged some of the most important data and ideas about how pain is generated. Wall was born in Nottingham, England, and educated at St. Paul’s, Oxford, and the Middlesex Hospital Medical School, from which he received his medical degree soon after the end of World War II. In 1948, he crossed the Atlantic, variously stopping at Yale, the University of Chicago, and Harvard Medical School, until in 1957 he set up shop at MIT for 10 years. From the early work with Lettvin, McCulloch, and Pitts emerged the first strands of his work on transmission in the spinal cord and the interaction between excitatory and inhibiting influences on sensory processing.’ His major early contributions were in the study of presynaptic inhibition, investigated
istorical Profile: Patrick D. Wall, DM, FRCP, FRS Clifford
J. Woolf
Editor’s note: As noted in the last issue, APS Journal plans to publish biographies of each winner of the Bristol-Myers Squibb Award for Distinguished Achievement in Pain Research. In 1988, Patrick D. Wall became the first recipient of this award. Clifford Woolf, MBBCh, PhD, MRCP, a colleague of Wall’s at University College London, contributed this biography.
299
Patrick D. Wall
300
BULLETIN
by the excitability changes produced during primary and the first recording of afferent depolarization,22 receptive field responses from dorsal horn neurons.23 Both gave rise to a torrent of work that is continuing. In the early 196Os, Wall began a collaboration with Canadian psychologist Ronald Melzack14 that reached an explosive pitch with the development of the spinal gate control theory.15 The impact of this work on neurobiologists and clinicians was immense and has changed forever the way in which we think about the sensation of pain. Wall’s logo, the model of Descartes, has been introduced at hundreds of lectures, to be knocked off its pedestal by his lucid arguments, to the fury of some thoroughgoing specificitists. The spinal gate control theory encapsulated work on the responses of neurons to particular types of afferent input17 and led directly to a novel form of pain therapy-transcutaneous electrical nerve stimulation4’ During the second half of the 1960% Wall continued analyzing the functional and structural organization of the spinal cord, examining its laminar patterns of connectivity and descending influences,24 activity in freely moving animals, 33 the response to visceral inputs2’ primary afferent terminations5 and the factors controlling receptive fields6 He also returned to England, invited by J. 2. Young to the Department of Anatomy and Embryology at University College London. There his work took on new directions, exploring the effect of deafferentation2g and introducing the concept of ineffective synapses,18 and in a dramatic flourish of papers, he began to study experimental nerve injury, the first serious investigation of neuropathic pain.34,42 Through his fascination with long-ranging afferent fibers in the spinal cord,43 he began to investigate the active responses of central neurons to dorsal root’11g*25 and peripheral nerve injury,2 leading to an investigation of the properties of cells in substantia gelatinosa37 and neuromas.26,3g A major aspect of his current work has returned to these long-ranging afferents. His work on peripheral nerve injury was based both in London and Jerusalem, where since 1972 he has been a visiting professor at the Hebrew University in Jerusalem and where his extremely productive and ongoing collaboration with Marshall Devor flowered.3s4*27 For such a strong individualist, Wall’s scientific work has been characterized by amazingly successful collaborations: with Melzack, continuing today with the jointly edited Textbook of Pain,36 with William Noordenbos,20~3g with Maria Fitzgerald,30-32,38
and with Stephen McMahon,*-I3 among others. I consider myself extremely privileged to be one of those.44-46 Apart from his work on acute and chronic pain mechanisms, Wall has played a major role in establishing pain as a serious scientific discipline through his editorship of the journal Pain. He also has brought the field to a wider audience through hisvery successful book, The Challenge of Pain, written with Melzack.” Most recently, he has co-written a book with Mervyn Jones for pain sufferers.35 Entitled Defeating Pain, it explains simply and directly the nature of the problem, to the understanding of which he has dedicated his career. In this article, I have selected only a tiny portion of Wall’s prodigious and ongoing work. Choosing a few works from so much material of quality and importance has turned out to be arbitrary, especially when one considers that Wall’s total output is close to 300 pieces and includes a paper published in Nature in 1947 on a rotating knife that causes brain lesions, a novel entitled Trio published in 1966, and many pithy and pertinent editorials including one in Pain that introduced the concept of preemptive analgesia.26 I hope this brief summary conveys some flavor of the man-sometimes irascible, often excessive, but always exceptional. Clifford Woolf is professor of neurobiology in the department of ana tomy and developmental biology, University College London.
References 1. Basbaum Al, Wall PD: Chronic changes in the response of cells in adult cat dorsal horn following partial deafferentation: the appearance of responding cells in a previously non-responsive region. Brain Res 116:181-204, 1976 2. Devor M, Wall PD: Reorganization of spinal cord sensory map after peripheral nerve injury. Nature 275: 75-76, 1978 3. Devor M, Wall PD: The effect of peripheral nerve injury on receptive fields of cells in the cat spinal cord. J Comp Neurol 199:277-291, 1981 4. Devor M, Wall PD: Plasticity in the spinal cord sensory map following peripheral nerve injury in rats. J Neurosci 1:679-684, 1981 5. Heimer L, Wall PD: The dorsal root distribution of the substantial gelatinosa of the rat with a note on the distribution in the cat. Exp Brain Res 6:89-99, 1968 6. Hillman P, Wall PD: Inhibitory and excitatory factors controlling lamina 5 cells. Exp Brain Res 9:284-306, 1969 7. Lettvin JY, Wall PD, Howland B, et al: Inhibition of impulses travelling in the primary afferent dorsal column fibres of cat spinal cord. Fed Proc 13:87, 1954
BULLETIN
8. McMahon SB, Wall PD: A system of rat spinal cord lamina 1 cells projecting through the contralateral dorsolateral funiculus. J Comp Neurol 214:217-223, 1983 9. McMahon SB, Wall PD: Receptive fields of rat lamina 1 projection cells move to incorporate a nearby region of injury. Pain 19:235-247, 1984 10. McMahon SB, Wall PD: The distribution and central termination of single cutaneous and muscle unmyelinated fibres in rat spinal cord. Brain Res 359:39-48, 1985 11. McMahon SB, Wall PD: Physiological evidence of branching of peripheral unmyelinated sensory afferents. J Comp Neurol261:130-136, 1987 12. McMahon SB, Wall PD: Descending excitation and inhibition of spinal cord lamina 1 projection neurones. J Neurophysiol59:1204-1219, 1988 13. McMahon SB, Wall PD: Changes in spinal cord reflexes after cross anastomosis of cutaneous and muscle nerves in the adult rat. Nature 342:272-274, 1989 14. Melzack R, Wall PD: On the nature of cutaneous sensory mechanisms. Brain 85:331-356, 1962 15. Melzack R, Wall PD: Pain mechanisms: a new theory. Science 150:971-979, 1965 18. Melzack R, Wall PD: The challenge of pain. Penguin Education, London, 1982 17. Mendell LM, Wall PD: Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres. Nature 206:97-99, 1965 18. Merrill EG, Wall PD: Factors forming the edge of a receptive field: the presence of relatively ineffective terminals. J Physiol 226:825-846, 1972 19. Millar J, Basbaum Al, Wall PD: Restructuring of the somatotopic map and appearance of abnormal neuronal activity in the gracile nucleus after partial deafferentation. Exp Neurol 50:659-672, 1976 20. Noordenbos W, Wall PD: Implications of the failure of nerve resection and graft to cure chronic pain produced by nerve lesions. J Neurol Neurosurg Psychiatr 44:1068-1073, 1981 21. Pomeranz B, Wall PD, Weber WV: Cord cells responding to fine myelinated afferents from visceral muscle and skin. J Physiol 199:51 l-532, 1968 22. Wall PD: Excitability changes in afferent fibre terminations and their relation to slow potentials. J Physiol 142:1-21, 1958 23. Wall PD: Cord cells responding to touch damage and temperature of skin. J Neurophysiol 23:197-210, 1960 24. Wall PD: The laminar organization of dorsal horn and effects of descending impulses. J Physiol 188: 403-423, 1967 25. Wall PD: The presence of ineffective synapses and the circumstances which unmask them. Phil Trans Roy Sot Lond B 278:361-372, 1977 26. Wall PD: The prevention of postoperative pain (editorial). Pain 33:289-290, 1988 27. Wall PD, Devor M: The effect on peripheral nerve injury on dorsal root potentials and on transmission of affer-
28. 29. 30. 31.
32.
33. 34. 35. 36. 37. 38.
39. 40. 41. 42. 43.
44.
45.
301
ent signals into the spinal cord. Brain Res 209:95-l 11, 1981 Wall PD, Devor M, lnbal R, et al: Autotomy following peripheral nerve lesions; experimental anaesthesia dolorosa. Pain 7:103-113, 1979 Wall PD, Egger MD: Formation of new connections in adult rat brains after partial deafferentation. Nature 232:542-545, 1971 Wall PD, Fitzgerald M: Effects of capsaicin applied locally to adult peripheral nerve. I. Physiology of peripheral nerve and spinal cord. Pain 11:277-363, 1981 Wall PD, Fitzgerald M: If substance P fails to fulfill the criteria as a neurotransmitter in somato-sensory afferents, what might be its function? In “Substance P in the nervous system,” CIBA Foundation Symposium 91, Pitman, London, 1982 Wall PD, Fitzgerald M, Nussbaumer JV, et al: Somatotopic maps are disorganised in adult rodents treated with capsaicin as neonates. Nature 295:891-693, 1982 Wall PD, Freeman J, Major D: Dorsal horn cells in spinal and in freely moving rats. Exp Neurol 19: 519-529, 1967 Wall PD, Gutnick M: Properties of afferent nerve impulses originating from a neuroma. Nature 248:740-743, 1974 Wall PD, Jones M: Defeating pain: the war against a silent epidemic. Plenum, New York, 1991 Wall PD, Melzack R (eds): Textbook of pain. 2nd ed. Churchill Livingstone, New York, 1989 Wall PD, Merrill EG, Yaksh TL: Responses of single units in laminae 2 and 3 of cat spinal cord. Brain Res 160:245-260, 1979 Wall PD, Mills R, Fitzgerald M, Gibson SJ: Chronic blockade of sciatic nerve transmission by tetrodotoxin does not produce central changes in the dorsal horn of the spinal cord of the rat. Neurosci Lett 30:315-320, 1982 Wall PD, Noordenbos W: Sensory functions which remain in man after complete transection of dorsal horns. Brain 100:641-653, 1978 Wall PD, Scadding JW, Tomkiewicz MM: The production and prevention of experimental anaesthesia dolorosa. Pain 6:175-182, 1979 Wall PD, Sweet WH: Temporary abolition of pain in man. Science 155:108-109, 1967 Wall PD, Waxman S, Basbaum Al: Ongoing activity in peripheral nerves: III. Injury discharge. Exp Neurol45: 576-589, 1974 Wall PD, Werman R: The physiology and anatomy of long ranging afferent fibres within the spinal cord. J Physiol (Lond) 255:321-334, 1976 Wall PD, Woolf CJ: Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol 356: 443-458, 1984 Woolf CJ, Wall PD: Chronic peripheral nerve section diminishes the primary afferent A-fibre mediated inhi-
302
BULLETIN
bition 77-85, 46. Woolf mary longed rosci
P
of rat dorsal horn neurones. Brain Res 242: 1982 CJ, Wall PD: The relative effectiveness of C-priafferents of different origins in evoking a profacilitation on the flexor reflex in the rat. J Neu6:1433-1442, 1986
ain History Musings William
D. Willis, Jr.
note: APS Bulletin has invited all the past presidents of the American Pain Society to share their views on the practice of pain management-past, present, and future. This issue features the reflections of William 0. Willis Jr., MD, PhD, the fourth president of APS, whose term ran from 7982 to 1983. Willis is Ashbel Smith Professor and Chairman, Department of Anatomy and Neurosciences, and Director of the Marine Biomedical Institute, University of Texas Medical Branch at Galveston. Editor’s
My Back Door Entry into the Field of Pain Research Although pain was one of the many nervous system topics that interested me as a medical student when I graduated from the University of Texas Southwestern Medical School in Dallas in 1960, the field I entered during my PhD training at the Australian National University in Canberra, Australia, in the laboratory of Sir John C. Eccles, MD, was the neuro-
William
D. Willis,
Jr.
physiology of motor control at the spinal cord level. Few, if any, basic science laboratories in the world at that time could be described as engaged primarily in pain research, but many were concerned with motor control. Most of the collaborative experiments with Eccles and Robert F. Schmidt, DrMed, PhD, were on presynaptic inhibition and included a study on the role of GABA. An important lesson was how to identify motoneurons innervating different muscles by antidromic activation. This method of identification also was applied in experiments on neurons that project in the dorsal and ventral spinocerebellar tracts. Although I was not involved in any published work on Renshaw cells or other types of interneurons, I did take note of the difficulties in studying interneurons. In a postdoctoral year at the physiology institute of Giuseppi Moruzzi, MD, in Pisa, Italy, my research background was broadened to include the neurophysiology of the brainstem reticular formation. Moruzzi’s group was working on the role of the reticular formation in arousal and the sleep-wake cycle, and France Magni, MD, and I examined the inputs from the cerebral cortex and spinal cord to antidromically identified reticulospinal neurons, using intracellular recording. Following my formal training period, I returned to Dallas as a faculty member in the department of anatomy. My first National Institutes of Health (NIH) grant was on the organization of muscle afferent connections to motoneurons of the cervical spinal cord, a topic that Robert Schmidt and I had begun to study in Canberra. While in Dallas, I interacted frequently with Parkhurst Shore, PhD, and Andres Goth, MD, in the department of pharmacology, and this stimulated an interest in the pharmacology of monoamines. Challenged by the suggestion of Madge and Arnold Scheibel’s that Renshaw cells don’t really exist, I did a collaborative study with my wife, Jean C. Willis, in which we made a primitive effort to mark the location of Renshaw cells and found that they were in lamina VII, rather than in lamina VIII, as the Scheibels had assumed. We contrasted the response properties of Renshaw cells with those of neurons located in lamina VIII and found that some of the latter projected rostrally toward the brain. This led to the idea of studying ascending tract cells in the ventral horn, and I decided to start with spinothalamic tract (STT) cells activated antidromically from the lateral thalamus. It turned out that STT cells in the cat lumbar spinal cord are concentrated in laminae VII and VIII. The reason for picking tract cells rather than interneurons was the difficulty in defining the role of