In the July issue of Practical Pain Management,¹ we covered the history of pain spanning the 17th and 18th centuries. Understanding the history of pain can help practitioners and researchers grasp the nature of pain, and demonstrate how the pain management specialty grew to include the current range of treatment options. This is the final installment of this series, and will review pain management practices from the 19th and 20th centuries.
Advances in the 19th Century: Pain Receptors
Scientific forces that had been building in the 18th century carried over to the 19th century, which saw an increased number of breakthroughs in the understanding of pain mechanisms and therapeutic innovations. The 19th century also saw physiology dominated by experimental research on the structure and function of primary organs, which plays a role in pain.² Lastly, after 40 years at the patients’ bedsides or in autopsy rooms, physicians began pursuing the study of pain symptoms. Medical texts in the early part of the 19th century started to focus on the links between physical and mental aspects of pain.²
The early part of the 19th century saw the development of clinics, which increased interest in the study of pain. Pain research and thinking at this time remained within the framework of “specificity theory” advanced by Johannes Müller (1801-1858) and later Maximilian von Frey (1852-1932), which saw pain as an independent sensation with its own sensory apparatus. In France, however, the Catholic Church again opposed materialism and spiritualism and was concerned that research was reducing the mental aspects of pain to a more physiological/chemical level. At this point in time, the Church wanted to keep the concept of “the soul,” which was introduced by René Descartes in the 17th century. According to Roselyne Rey, this conflict prevented a more complete understanding of pain, and it hardened the positions of each side.²
Despite religious objections, the pace of research continued.
Johannes Müller
According to Rey, advances in microscopy benefitted the work of Johannes Müller, who lived and worked in Germany. Müller concluded that there were specific energies within the nerve fiber and that the paths of nerve fibers were rigorously ordered. This research led to his summation that there were specific fibers for pain or receptors (neuroreceptors) for painful sensations. As noted, this finding was a major step forward in understanding pain transmission and led to Müller formulating the law of specific nerve energies.
Müller used amputees in his research, since all the primitive fibers were found at the level of the stump, and the nerve trunk remained intact. In his studies, he examined the effects of a stimulus that was applied to an area restricted to the branches of the nerves found below the stimulation point. The sensations received by the brain were the same as with the stump intact.²
Müller then proposed a model where each posterior root ganglion would function like a semiconductor of the sensation. This model may represent the first step toward the concept of a “gate,” which will be discussed in more detail in the findings of the 20th century. Müller believed that the reaction of a feeling produced by a sensory nerve would occur in the sensory nerves and not the motor nerves. He stated that, “the central parts of the sensory nerves that transmit to the brain are capable of feeling independently of the nerve cords or conductors. Sensations are determined appropriate to each sense.”²
Müller proposed a theory for pain, which took into account findings from physiology, historical observations, pathology, and integrated psychological dimensions of pain. He believed that pain was not imaginary, that pain could occur without an external stimulus.²
His thinking was similar to that of Pierre Jean George Cabanis, which we discussed in Part 1, who felt that pain sensations could be generated spontaneously in the brain and provoke pains that were real.¹ Müller’s conclusions about pain were important findings and can be traced back to Descartes’ models of pain transmission (The Boy and Fire). Müller’s model encompassed significant scientific advances largely due to the improvement of the microscope.
Middle of the 19th Century
In the middle of the 19th century, there was a debate over whether pain could be avoided or accepted fatalistically (ie, whether it was predetermined by fate). This debate was prompted by the role of war, which promoted further progress in the understanding of pain. Fatalism implies that we do not choose pain, but that it happens anyway—as in the case of war. As a result of lessons learned on the battlefield, many new treatment options were introduced in England, France, and the United States, including nitrous oxide, the isolation of morphine in Germany, and ether in the United States.
Toward the end of the 19th century, research started to focus on receptors that were specific for pain. The advanced microscopes allowed the identification of neural structures, which were very different from one another. Müller felt that these structures served very different functions. This research trend represented another major step toward the theory of specificity.²
Maximilian von Frey
Maximilian von Frey (1852-1932) elaborated on the work of Müller. However, von Frey’s work had very different implications, and led to a more restricted concept of pain.
He was trying to identify particular points on the skin, which responded specifically to one of the four cutaneous sensations: touch, heat, cold, and pain. In order to accomplish this task, he invented what he called an aesthesiometer, where the stimulus consisted of hair.
The result did not depend on pressure alone, but on location. Further, von Frey felt that pain was perceived when the stimulus went beyond a certain threshold, and this led to his conclusion that pain results from the stimulation of special organs. Von Frey’s theory was based on the mechanisms of pain that he felt were dependent on a specific neural apparatus. Today, von Frey’s theory has been generally discounted, but his work contributed to the understanding of sensory receptors and the measurement of insensitivities of stimuli and sensory thresholds.²
According to Rey, every attempt to establish the notion of specificity at the fiber or receptor level, including transmission, turned out to be insufficient in understanding pain. The methodology of reductionism led to the basic explanation that pain is a simple response to a stimulus.²
Bridging the 19th and 20th Centuries: Pain Stimulus
Alfred Goldscheider
Toward the end of the 19th century, and the beginning of the 20th century, the work of Alfred Goldscheider (1858-1935) greatly contributed to the understanding of pain. Much of the research at the time focused on looking for specific pain points and associations. This focus of research did not generate positive results, the lack of which led Goldscheider to propose a different theory based on three types of research findings²:
The first research finding was that the increase of pain upon repeated applications of a stimulus was out of proportion with the intensity of the stimulus. Goldscheider believed this cumulative process acted at the spinal cord and the brain. In my opinion, this finding appears to be the first mention of what is now considered central sensitization.
Second, he found that when pressure was applied to the skin with the head of a pin, the subject initially felt pressure, followed shortly by the sensation of pain.
Finally, he found that there were areas devoid of pressure points, which turned into pain points.²
Goldscheider tried to find an explanation regarding the intensity of the stimulus, which brought him back to the theory of “central summation.” In 1920, he published a collection of his work, which he began in 1898. He postulated that the difference perceived by tickling, touch, and pain was not due to specific receptors, but due to the bifurcation of the nerve fibers and the routes from the periphery to the center through posterior horns. He felt there would not be specific fibers for pain, but special pathways that depended on stimulus intensity. The more frequently a receptor or fiber reacted in a given direction, the more the effects of stimuli would tend to take this path.
I believe his work was a significant step forward and inspired a number of theories in the 20th century, including the gate control theory of pain. The transition of knowledge from one century to another does not move forward in large steps, but builds momentum, similar to a large wave gaining force as it nears land. The ideas that were produced throughout the 19th century set the stage for major developments in our understanding of pain in the 20th century. The concept that peripheral receptors were structurally diversified and specialized was now accepted, although the existence of specific pain receptors had not yet been discovered.
The 20th Century: Temporal Aspects of Pain
At the beginning of the 20th century, pain research focused on problems of communication, speed, and efficiency.² There were two dominant pathways that pain research focused on during the first half of the 20th century.
First was the temporal aspect of pain mechanisms. This shifted the focus from specific receptors, transmission pathways, and central organs to time and space factors, conduction rate of nerve impulses, and the study of temporal summation. This shift included studying the connection between mental processes and pain, both intellectual and emotional.
The second major focus came about with the introduction of Darwin’s theory of evolution. It introduced the notion of adaptation in the transmission of sensations and viewed the nervous system as a defense against aggression.²
At the beginning of the 20th century, knowledge of pain had reached a new level. The Zeitgeist within the world of research moved forward now that the influence of the Church was subsiding.
Henry Head
This evolutionary movement in knowledge set the stage for Henry Head (1861-1948). In 1911, he proposed a model indicating the relationship between the cortex and the thalamus based on his observation of the thalamic syndrome. He felt that thalamic lesions seemed to modify the emotional or affective tone to any perceived sensation. He concluded that the thalamus appeared to influence or amplify sensations transmitted by afferent tracts.
Head determined that the major function of the thalamus was the terminus for all afferent sensory pathways, which were then redistributed in two directions:
First, to the cortex and the body of grey matter in the thalamus.
Second, that this grey matter represented the center for certain sensations and complemented the sensory cortex.
The lateral portion of the thalamus served as a receiving station for fibers from the cortex, leading Head to believe that the optic thalamus was the center of consciousness.³
Head felt that the sensation of pain could not be explained with a linear theory of pain. This idea was introduced by Müller in the 19th century, but Head’s research gave it more credibility. His model has continued to influence pain research throughout the 20th century and emphasized the dynamic connections between various levels, which can be observed by the gate control theory of pain theorized by Ron Melzack and Patrick Wall.
Finally, Head’s work should be remembered for its recognition of the role of evolution and that man’s evolutionary goal was to ultimately control his emotions and instincts.
Charles Sherrington
The work of Charles Sherrington (1857-1952) was another major contribution to the study of pain in the 20th century. He was a Cambridge neurophysiologist whose best-known work was the Integrative Action of the Nervous System, published in 1908, in which he transposed the theory of evolution to the level of the neuron and the synapse. He coined the term “synapse” for the space separating two neurons. Sherrington studied the integration of the nervous system. He focused first on the simple reflex arc, which is the composite action resulting from several coordinated reflexes. He studied the simple reflex arc unit’s construction, which was the predecessor of the motor unit concepts. Sherrington concluded that the nervous system did operate as a single integrated whole and received the Nobel Prize for physiology or medicine in 1932 as a result of his work.
The simple reflex was the first step in this coordinated nervous system process. Sherrington believed that the activity produced by the effector was the appropriate response to the stimulus transmitted by the receptor, which called several neurons into play. “The main function of the receptor is to lower the excitability threshold of the arc for one kind of stimulus and to heighten it for all others.”²˒⁴
Sherrington classified stimuli on the basis of their origins into three categories:
Proprioceptive receptors—stimuli arising from organs deep in the body, muscles, joints, tendons, and blood vessels.
Exteroceptive receptors—found over the entire surface of the body.
Interoceptive receptors—includes digestion and absorption known as the visceral sense.²
Sherrington’s body of work represented a major step forward that moved pain research away from specificity to a more global approach. Further, his work reinforced the role emotion played at the site of the nociceptor.⁴
Edgar Douglas Adrian
Electrophysiology was an important development in the early 20th century. The most significant development, however, was the cathode ray oscillograph, which was helpful in understanding that nerve propagation was dependent upon changes in nerve excitability and conductivity. Edgar Douglas Adrian (1889-1977), who published The Basis of Sensation in 1928, contributed to these developments² and shared the Nobel Prize in 1932 with Charles Sherrington for work on the function of neurons.
By using the oscillograph, Adrian’s research focused on how quickly stimulus generated an electrical current that would result in pain and how long that pain would last. He concluded that nerve impulses do not travel at the same speed—a concept that proved decisive in identifying pain fibers. Adrian surmised that the duration and intensity of painful stimulus would go through a “summation” process in order to reach the central nervous system (CNS), but brief stimuli would not. The intensity of the painful stimulus was also dependent on the size of the fiber, a finding that was consistent with the all-or-none law first established in 1871, which states that a weak or strong stimulus both produce nerve impulses of the same strength.²
Advances in electrophysiology also assisted Thomas Lewis, of London’s University College Hospital, in 1942, to conclude that there were two types of fibers responsible for transmitting pain to the CNS, some fast and others slow.² The advances in electrophysiology during this period led to the identification of specific pain fibers that is still used today.
As research and thinking progressed through the 20th century, we see a shift away from specificity theory toward a more global approach. As we approach the “club house turn” with the gate in sight, we now consider the next major contributor, William K. Livingston.
Approaching the Gate
William K. Livingston
In 1989, I helped start the multidisciplinary pain program at Oregon Health & Science University (OHSU), which was associated with the Department of Anesthesiology. At that time, I was not aware that the first multidisciplinary pain program was started at the University of Oregon Medical School (later to become OHSU) in the late 1940s under the direction of William K. Livingston (1892-1966). During World War II, Livingston joined the Navy as a surgeon and became interested in peripheral nerve injuries. Soon after, he became head of the Oakland Naval Hospital’s Division of Peripheral Nerve Injuries. He published his first book, The Clinical Aspects of Visceral Neurology, in 1935, and then Pain Mechanisms in 1943.
In 1947, Livingston accepted the position of Chairman of the Department of Surgery at the University of Oregon Medical School. One of his conditions for accepting this position was that he could start a “pain project” in which a team of investigators would conduct research on the physiological and psychological aspects of pain. Among the first fellows Livingston hired was a young psychologist by the name of Ron Melzack. His team decided “as our basic assumption the concept that nothing can properly be called pain unless it is consciously perceived as such.”⁵ Operating under this principle, Livingston opened the aperture further than anyone we have discussed. He considered pain a perception, not a simple sensory event.
By the 1950s, Livingston’s thinking had evolved from exploring sensory nerve pathways to a broader interpretation of brain function and its relationship to the perception of pain. “Pain is not always measurable in terms of stimulus intensity. Because we now know that the brain has the power to suppress the sensory signal before it can ascend to the brain.” Further, he emphasized that “emotional states can augment the perceptual impact, and that it is a dynamic process that is constantly being tuned to the needs of the individual from moment to moment.”⁵
Livingston and his team concluded that pain was not mechanistic and suggested that pain was the direct result of activation of specific sensory receptors at the body periphery, which appeared to be higher up along the conducting pathways within the CNS. Their evidence showed that the pain and temperature tract in the spinal cord was not the sole route by which pain signals could ascend to perceptual levels, because signals could take many indirect routes and bypass any point of interruption on any given tract. Finally, his research indicated that the cerebral cortex was not the true center for pain perception, as responses to noxious stimuli could take other routes to the core of the brain to reach subcortical structures and areas of the cortex outside the somatosensory region. He felt that the brain exerts a downstream influence on all sensory input.⁵
Physiology vs Psychology: Repudiating the Either/Or Dichotomy
In Pain and Suffering, Livingston wrote extensively about the role of psychology and pain, talking about the difficulty encountered in the search for a satisfactory definition of pain. He felt that any definition of pain could not be considered from either a physiological or a psychological approach. Any consideration of pain by one approach alone or without due regard to the other is incomplete.⁵ He was avoiding the old dualistic dichotomy, or what I refer to as the either/or school of thinking.
Livingston strongly believed that pain is a perception, it is subjective and individual, and it varies in different races. Individual susceptibility to pain may also vary with changes in emotions and physical equilibrium. For Livingston to classify certain types of pain as “psychic” pain is purely arbitrary because all pain is a psychic perception. Further, Livingston cautioned against the rather widespread tendency to use this term loosely to apply to cases in which there is not an obvious organic origin for the pain.⁵
In my opinion, he is closing the door on the dualistic notion of conversion as proposed by Sigmund Freud and others throughout the past two centuries. Although, it is interesting to note that in the Diagnostic and Statistical Manual of Mental Disorders (DSM) I, it was called conversion,⁶ and in the DSM IV, it is referred to as somatoform pain disorder.⁷ This still implies conversion.
The Vicious Cycle of Pain
Livingston also wrote about the vicious cycle of pain (causalgia). He states that, “An organic lesion at the periphery involving a sensory nerve may be the source of constant irritation. Further, that afferent impulses from the ‘trigger point’ eventually create an abnormal state of activity in the internuncial neuron centers [neurons that conduct impulses from afferent neurons to efferent neurons] of the spinal cord gray matter. This disturbance is then reflected in an abnormal motor response from both the lateral and anterior horns. This muscle spasm, vasomotor changes, and other effects, which the central perturbation of function brings about in the peripheral tissues, may contribute new sources for pain and new reflexes. A vicious cycle of activity is created. If this process is permitted to continue it spreads to new areas and acquires momentum that is increasingly difficult to displace.”⁵
Ron Melzack
Patrick Wall
Ron Melzack, Patrick Wall, and the Gate Control Theory of Pain
The gate control theory of pain, which was springboarded by Livingston’s influence, represents a model of pain that is contrary to the dualism school of thinking and the specificity theory of pain, which is still taught in many US medical schools. In 1965, Ron Melzack (1929-present) and Patrick Wall (1925-2001) proposed this theory, which suggests that neural mechanisms in the dorsal horn of the spinal cord could act as a gate, increasing or decreasing the flow of nerve impulses from peripheral fibers to the spinal cord cells projecting to the brain. In other words, the spinal cord “gate” either blocks pain signals or lets them pass onto the brain.
Gate Control Model
Melzack and Wall stated that somatic input is subjected to the modulating influence of the gate before it evokes pain perception and response. This theory suggests that large fiber inputs, such as gentle rubbing or vibration, close the gate, while small fiber inputs (evoked by intense stimulation) generally open the gate, which is influenced by descending controls from the brain. It further proposes that the sensory input is modulated at successive synapses from the spinal cord to the brain. Pain occurs when the number of nerve impulses arriving at these areas exceeds a critical level (Figure 1).⁸
The Motivational Component of Pain
In 1968, Melzack, with his colleague Kenneth Casey, extended the gate control theory to include the motivational component of pain. In this model, there are three components described as the sensory discriminative system, the motivational/affective system, and the cognitive/evaluative system (Figure 2).
The sensory component—the discriminative dimension of pain—is influenced primarily by the rapidly conducting spinal systems.
The powerful motivational and unpleasant affect component of pain, which is subserved by activities of the reticular and limbic structures that are influenced primarily by the slow conducting spinal systems.
The neocortical or higher CNS processes, such as cognitive evaluation of the input in terms of past experiences, which exerts control over both discriminative and motivational systems.
Melzack and Casey assumed that all three components interact with one another to provide perceptual information that ultimately influences the motor mechanisms characterizing pain.⁹
Motivational/Affective and Sensory Discriminative Systems
The output of the T cells (transmission) projects to the sensory discriminative system and the motivational/affective system. The central control trigger is represented by a line running from the large fiber system to central control processes; these in turn project back to the gate control system and to the sensory discriminative and motivational/affective systems. All of these systems interact with one another and project to the motor system.⁸
The strength of this model is that it is not linear; it incorporates several systems in a coordinated fashion and includes the emotional aspects of pain as represented by the motivational/affective system. In neuro-anatomical terms, this model opened the aperture to include neocortical influences in addition to limbic influences, and showed how they communicated with each other in an integrated fashion.
Research suggests that the motivational/affective dimension is under the influence of the brainstem reticular formation and the limbic system, which play important roles in pain. Further, cognitive issues have a profound effect on the pain experience by influencing sensory input in terms of memory, before it activates the discriminative or motivational systems.
Melzack and Wall proposed that the dorsal column pathways act as a feed-forward limb of this loop and that these rapidly conducting ascending and descending systems can account for the fact that psychological processes play a powerful role in determining the quality and intensity of pain.⁸
Today, the gate control theory continues to thrive and evolve despite considerable controversy. The concept of gating is stronger than ever. The technology of spinal cord stimulation is also based on the gate control theory.
Conclusion
This article series should be considered as an overview of the history of pain. Our journey covered four centuries from Descartes to the gate. I have imposed arbitrary parameters and left out many contributors who have played an important role in adding to our understanding of the pain experience. I attempted to include the major contributors who appeared to build on one another’s work. There were false leads, as in the case of von Frey’s work, but his work stimulated new thinking and was significant for that reason. I also included the research that led to the specificity theory and the response to that model, which is still in use today. The framework for this article came largely from Roselyne Rey’s book, The History of Pain, up until the 20th century. The inclusion of Livingston was my responsibility alone, based on my reading and understanding of his work and the influence it had on the gate control theory. From a historical perspective, it is appropriate to end this journey with the 20th century, as it is too early to evaluate the contributions that the 21st century will produce.
Note: All of the major contributors covered in this article are available online. For those of you who are interested in more information about the history of pain, I would recommend that you visit The John Liebeskind History of Pain Collection at the Louise M. Darling Biomedical Library at the University of California, Los Angeles.