The Anatomical Basis of Pain

The concept that the mind and the body are separable but interconnected, known as dualism, is commonly attributed to Rene Descartes. He described the mind as a nonphysical substance and distinguished the mind from the brain, which was physical (Descartes 1641). In his 1649 essay, "The Passions of the Soul," Descartes sought to delineate emotions from physiological processes and reductionistically compared the human body to a watch:

... the difference between the body of a living man and that of a dead man is just like the difference between, on the one hand, a watch or other automaton (that is, a self-moving machine) when it is wound up and contains in itself the corporeal principle of the movements for which it is designed ...; and, on the other hand, the same watch or machine when it is broken and the principle of its movement ceases to be active (Descartes 1664).

The philosophical mind-set of mechanism, suggesting that the human body functions as a simple machine, with pain being the result of its malfunction (Sawda 2007) was the outcome. This idea, the extension of which informs much of our current day scientific inquiry and clinical practice, had been evolving slowly over time and ultimately superseded more traditional philosophical and theological explanations of pain. Beginning with the early anatomical studies of Galen of Pergamum (130-201 AD) and Avicenna, the Persian polymath (980-1037 AD), evidence for a physical, visible basis of pain developed. During the Renaissance, the Zeitgeist of the day encouraged questioning and cultural mores evolved to view science less as religious heresy. This change permitted scientific observation and inquiry, yielding advances in the anatomical, medical, and neurological knowledge. The study of the circulation of blood by William Harvey in 1628 (Harvey 1628), and the direct anatomical studies of Descartes in 1662 (Cranefield 1974) elucidating sensory physiology, became the theoretical basis for further exploration in the 18th and 19th centuries through today (Fig. 1.1).

In the years that followed those early anatomical observations, several important ideas added to our understanding of physiologic pain, including the specificity theory, pattern theory, summation theory, and gate theory.

Descartes described the concept of a pain pathway and theorized the transmission of pain signals, as illustrated in Fig. 1.2. Nearly 150 years later, Charles Bell in Scotland proffered the specificity theory. Specificity theory, the seminal concept that pain has a dissectible and demonstrable anatomical basis, and that individual sensory nerves exist and are specialized to perceive and transmit information from an individual stimulus type, cleared the initial path for considerable subsequent experimentation (Bell 1811). Bell discovered that ventral root stimulation caused motor contraction. In 1839, Johannes Muller advanced the idea of specialization of nerve fibers, considering the sensation of sound to be the "specific energy" of the acoustic nerve and the sensation of light the particular "energy" of the visual nerve (Muller 1839). In 1858, Moritz Schiff demonstrated a reproducible loss of tactile and painful sensation resulting from particular lesions of the spinal cord. In 1882, Francois Magendie demonstrated that sensory function occurred via stimulation of dorsal nerve roots (Bell 1811,

Figure 1.1 Rene Descartes (1596-1650) described the first systematic accounts of the mind/body relationship and mechanisms of action of sensory physiology. In this drawing, he depicts light entering the eye and forming images on the retina. Hollow nerves in the retina would then project to the ventricles, stimulating the pineal gland to release animal spirits into the motor nerves to initiate movement.

Figure 1.1 Rene Descartes (1596-1650) described the first systematic accounts of the mind/body relationship and mechanisms of action of sensory physiology. In this drawing, he depicts light entering the eye and forming images on the retina. Hollow nerves in the retina would then project to the ventricles, stimulating the pineal gland to release animal spirits into the motor nerves to initiate movement.

Magendie 1822). Ultimately, the sum of these and other discoveries was the specificity theory's advancing the idea of specific pathways and specific receptors for pain that continues to inform our thinking today.

The pattern theory was introduced by Alfred Goldscheider, a German army physician, in 1894. This theory proposed that particular, reproducible patterns of nerve activation were triggered by a summation of sensory input from the skin in the dorsal horn. Prior to this time, the skin was believed to be endowed with only one kind of sensation. However, Goldscheider demonstrated that skin contains several distinct perceptive organs. He described three distinct stimuli, pressure, warmth, and cold, and showed that localized points reacted only to a given stimulus and each point had a specific function (Goldscheider 1884). Nafe expanded the pattern theory to the concept that a perceived sensation is the result of spatially and temporally patterned nerve impulses rather than the simple conduction of an individual or specific

Figure 1.2 Descartes reduced reflex nerve function to hydraulic mechanisms, stating, "If the fire is close to the foot, the small parts of this fire, which...move very quickly, have the force to move the part of the skin of the foot that they touch, and by this means pull the small thread... opening the entrance of the pore, where this small thread ends...the entrance of the pore or small passage, being thus opened, the animal spirits in the concavity enter the thread and are carried by it to the muscles that are used to withdraw the foot from the fire."

Figure 1.2 Descartes reduced reflex nerve function to hydraulic mechanisms, stating, "If the fire is close to the foot, the small parts of this fire, which...move very quickly, have the force to move the part of the skin of the foot that they touch, and by this means pull the small thread... opening the entrance of the pore, where this small thread ends...the entrance of the pore or small passage, being thus opened, the animal spirits in the concavity enter the thread and are carried by it to the muscles that are used to withdraw the foot from the fire."

receptors or pathway (Nafe 1929). Later, the pattern concept was further detailed by Sinclair and Weddell in 1955, who believed that all sensory fiber endings, except those innervating hair follicles, are similar, and it is the pattern of their activation that was felt to be necessary for sensory discrimination (Sinclair 1955, Weddell 1955).

The specificity theory or the pattern theory alone, or in combination could not fully explain many of the clinical observations that have been made about pain. Particularly confounding were the presence of discontinuous pain fields and the capacity for the development of hyperalgesia, the ability to increase pain sensitivity with repeated stimulation. It was also known that pressure sensation over time resulted in increased painful sensation and that pressure points could respond differently to stimulation than did adjacent areas (Perl

2007). Thus, the summation theory was proposed to explain these phenomena. Summation theory is based on the idea that there exist multiple interactions between and among neurons, not only within the sensory system, but also including overlap and contributions to pain sensation from internuncial neurons and the autonomic nervous system. The importance of these interactions was demonstrated by Livingstone, Hardy, and Wolff. In 1932, Dr. Charles S. Sherrington was awarded the Nobel Prize in Medicine for his development of the concept of the motor unit, comprised of a receptor, conductor, and effector; and he later identified polymodal receptors and selective excitability. These ideas are central to explaining the anatomy of the summation theory and began to examine the wide array of pain responses and great capacity for neuroplasticity that are well known in the clinical arena. These concepts, which Sherrington initially published in 1906, are still highly relevant today (Sherrington 1906).

In 1965, the ground-breaking gate theory was published by Canadian psychologist Ronald Melzack and British physiologist Patrick Wall (Melzack and Wall 1938) and remains a dominant theory in explaining many of the interrelationships seen in pain sensation and perception. Central to this theory is the concept of the presence of a "gate" that either permits or stops the conduction of a given pain signal based on intermodulation and summation of both painful and nonpainful nerve messages, by either turning on or off an inhibitory interneuron. The gate theory permitted the integration of the presence of specific pathways, patterns, and summation of stimuli and provided a paradigm through which to view the more complex interaction between the central and peripheral nervous systems. Despite the fact that many of the specific details of the theory were later refuted, gate control's central tenet of pain modulation through both central mechanisms and competing stimuli has allowed for a more complex understanding of pain and provides the basis for a considerable volume of current day research as well as pain therapy.

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