CHAPTER 16 Basic science on somatovisceral interactions

peripheral and central evidence base and implications for research

Introduction

The basic philosophy of osteopathic medicine is a ‘whole-person’ approach to care and to the understanding of the integrative functioning of the body. This approach is also the basis of so-called ‘holistic’ or ‘integrative’ medicine (see Chapter 1). It is included both implicitly and explicitly in all manual therapy or other physical interventions directed at the body in the treatment of dysfunctional states (as practiced by chiropractors, physical therapists, massage therapists, and others). This approach uses the biological mechanisms of the body and brain to correct the pathophysiological regulations of the body tissues (see Chapter 1). Beal (1985) described this focus in a more practical and direct way: ‘The concept of viscerosomatic reflexes reflects the strong interest of the osteopathic profession in the relationship of the musculoskeletal system in health and disease. It was apparent to early practitioners in the profession that somatic dysfunction was the result of multiple factors – somatic, visceral, and psychologic…. [Thus] The osteopathic profession has held certain basic tenets to be true – that altered or impaired function frequently occurs in the somatic system, that these somatic components may be manifest as presymptomatic signs of disease, and that they may be expressed as local or remote effects of dysfunction as somatovisceral or viscerosomatic reflexes. … [Therefore] osteopathic manipulative treatment of viscerosomatic reflexes has been advocated on the basis that it is designed to reduce somatic dysfunction, to interrupt the viscerosomatic reflex arcs, to influence the viscus through stimulation of somatovisceral effects, and to reduce the potential preconditioning effect of somatic dysfunctions to body stressors’.

The physiological and hence also the pathophysiological regulation of body tissues involves the brain and its reciprocal communications with the body. The efferent pathways from the brain are the somatomotor, autonomic, and neuroendocrine systems. The afferent pathways from the body tissues to the brain are the large groups of small-diameter (Aδ- and C-) afferents, which monitor the mechanical, thermal, metabolic, and inflammatory states of the tissues (see Chapter 2 and Fig. 2.1).

Manual and other physical interventions at the somatic body tissues do affect the target tissues locally, independent of their innervation on one side (see Chapter 6) and the somatic afferent innervation of these tissues on the other. The consequences of these therapeutic interventions are complex, as stimulation of the afferent neurons activates (1) reflex circuits in the spinal cord, brain stem, and hypothalamus involved in regulation of somatomotor, autonomic, and endocrine systems; (2) neural pathways and centers related to interoceptive body sensations, which include pain, heat, and other sensations from the skin, and pain and other sensations from deep somatic tissues and viscera; and (3) neural circuits related to affective (emotional) feelings.

How do we bring these levels of neural integration together to understand the mechanisms underlying the potentially curative effects of manual interventions on functional disorders in the deep somatic and visceral body domains? Some mechanisms underlying the neural processes potentially operating during manual therapy are discussed in the chapters of this book. Here I will critically discuss the experimental measurements and clinical observations on which the concepts of somatic dysfunction and the dysfunctional spinal segment are based. This includes the concept of somatovisceral interactions. I will concentrate particularly on the spinal autonomic (largely sympathetic) systems. Then I will summarize some aspects of the integrative functions of the spinal cord and potential mechanisms underlying chronic deep somatic and visceral pain. Finally, I will discuss the role of positive feedback mechanisms involving the somatomotor and spinal autonomic systems. I will not address the philosophical superstructure of osteopathic medicine that is related to ‘spirit, mind, brain and body’ (but see Introduction and Figure 2.1 in Chapter 2).

Systems and mechanisms involved in manual therapy

Various systems believed to be important in understanding the effectiveness of manual therapy in osteopathic medicine (but also in other medical fields independent of osteopathic medicine) and various underlying mechanisms have been discussed in this book. The common theme in all chapters (with the exception of Chapter 6) is that the integrative action of the central nervous system (which includes the spinal cord!) stands in the center to provide the mechanisms operating in manual therapy. Here I highlight the main topics that have been discussed:

1. Use of the body’s recuperative power and the promotion of self-healing in the therapeutic approach of manual medicine (Chapters 1 9 10 12 13 15).

2. Integration of brain, body, and mind in the holistic (integrative) approach of manual medicine. Manual medicine as part of complementary and alternative medicine (Chapters 1 11 12 15).

3. The role of the musculoskeletal system, including joints, fascia, and other deep somatic tissues of the spine in the generation of dysfunctional states of deep somatic tissues and viscera, and in the curative effects of manual therapy (Chapters 1 3 7 12 13 14).

4. Close interaction between the somatic body domain (in particular deep somatic) and the visceral body domain (somatovisceral interaction) (Chapters 2 3 4 7 8 12 13).

5. Regulation of autonomic targets in the viscera, deep somatic tissues, and skin by the sympathetic nervous system (Chapters 2 3 4 5 7).

6. Integration of afferent information from deep somatic tissues (in particular skeletal muscle, fascia, and joints of the spine) and its control by supraspinal centers. This integration is believed to be essential in the curative effects of manual therapy to induce changes in the motor systems (skeletal muscle, targets of the sympathetic nervous system) and in the ascending systems related to body sensations, including pain (Chapters 2 3 4 7).

7. Chronic pain in deep somatic tissues (in particular skeletal muscle, fascia, and joints) and viscera. This pain is related to the activation of small-diameter spinal (and trigeminal) afferents from deep somatic tissues (in particular the spine) and viscera, and integrative mechanisms of the central nervous system (Chapters 2 6 7 13 14).

8. Systemic effects of manual therapy based on central integration of neural regulation of skeletal muscle by the somatomotor system, neural regulation of viscera, blood vessels,and other targets by the autonomic nervous system, neuroendocrine regulation in stress and antistress, and neural regulation of pain behavior (Chapters 7 8 9 10).

Somatic dysfunction and the spinal segmental dysfunction

The scientific basis of osteopathic medicine is related to pathobiological ¹ processes in deep somatic tissues, in particular of the spine, and in the viscera; to the role of the afferent and efferent (somatomotor and autonomic) innervation of the diseased tissues; to the integrative neural processes in the spinal cord; and to supraspinal control. This is reflected in the osteopathic practice that consists – to put it simply – of the diagnosis and treatment of (1) structural changes in deep somatic tissues of the spine; (2) restricted mobility of skeletal muscle, joints, and fascia; and (3) changes in soft tissue consisting of alterations of local circulation, muscle tone, deep tissue sensitivity (discomfort and pain); and texture of deep tissues (‘trophic changes’) (Johnston 1992, Patriquin 2003; see Chapter 12). Interactions occur between the neural and non-neural components, between different deep somatic compartments, between deep somatic and visceral tissues, and between spinal and supraspinal neural circuits. Improvements in the diagnosis and treatment of functional diseases depend greatly on our understanding of the mechanisms of these interactions. In the center of both stands the concept of somatic dysfunction (previously called osteopathic lesion) and the concept of spinal segmental dysfunction (also called lesioned segment, or dysfunctional segment or facilitated segment).

The scientific basis of the ‘philosophy of osteopathy’ as it is propagated today (Chila 2010; Chapter 1 in this book) was first formulated in its full extent by Korr in 1947 and 1948, and has remained practically unchanged up to the present (Korr 1947, 1948, 1955a,b, 1978, 1979). For example, his keynote article published in 1948 in the Journal of the American Osteopathic Association was reprinted in the same journal in 2000 without further comments or interpretations in the light of modern research.² Korr himself has directed and conducted research in this field, in particular related to spinal sympathetic outflow, in order to give support to his concept (Korr et al. 1958, 1962, 1964, Wright et al. 1960). Korr’s scientific ideas and research are mainly rooted in the experimental work of Denslow on the somatomotor system (Denslow 1944; Denslow & Clough 1941; Denslow & Hassett 1942; Denslow et al. 1947) and in the experimental work of Kellgren and Lewis on referred pain and hyperalgesia in the deep somatic tissues and viscera (Kellgren 1938, 1939, 1940, Lewis & Kellgren 1939, Lewis 1942).

The neural concept underlying osteopathic medicine

In the paper ‘The neural basis of the osteopathic lesion’, Korr (1947) states (I quote this because it makes clear what Korr foreshadowed in his future research and in his overall concept [bold and explanations in squared brackets are from me]):

Four of the main principles in osteopathy appear to be:

1. Joints and their supports are subject to anatomic and functional derangements.

2. These derangements have distant as well as local effects.

4. They may be recognized, and their local and distant effect influenced favorably by manipulation.

Accepting the existence of joint derangements (osteopathic lesions), it is our purpose in this paper to examine not the mechanical and etiological factors involved, but rather the fundamental basis for principle 2 and 3 [i.e. the neural basis of these principles] and to a small extent principle 4,…

The osteopathic lesion has many aspects which are partly revealed in the local and distant effects referred to as principle 2. Included among these are:

1. Hyperesthesia, especially of the muscle and the vertebrae [i.e., pain and hyperalgesia].

2. Hyperexcitability, reflected in altered muscular activity and in altered states of muscle contraction.

3. Changes in tissue texture of muscle, connective tissue, and skin [trophic changes].

4. Changes in local circulation and in the exchange between blood vessels and tissues.

5. Altered visceral and other autonomic functions.

How are these effects produced? What are the central factors [factors depending on the central nervous system] responsible for these manifestations of structural and postural abnormalities? What in the intrinsic nature of the osteopathic lesion is the basis for the peripheral, palpable, and clinical effects? What fundamental [neural] changes take place as a result of effective manipulative therapy? [To date, none of these questions have been answered].

After an extensive discussion Korr concludes:

An osteopathic lesion represents a facilitated segment of the spinal cord maintained in that state by impulses [in primary afferent neurons] of endogenous origin entering the corresponding dorsal root. All structures receiving efferent nerve fibers from that segment are, therefore, potentially exposed to excessive excitation or inhibition.

Under the heading Manipulative Therapy at the end of the paper, Korr states:

…Since the excessive tendinous and muscular tension produced around a joint, let us say, by some bony displacement tends reflexly to produce more tension, the manipulative easing of tension breaks a vicious cycle [involving skeletal muscle, its afferent and efferent innervation, and the spinal cord; see pages 289–291].

Still another type of vicious cycle may be in operation and be broken by manipulative therapy… Through overexcitation of sympathetic fibers in the segment of lesion, visceral pathology may be established. The anterior horn cells may then be subjected to additional bombardment with impulses conveyed by visceral afferents, thus causing exaggeration of the somatic lesion … Manipulative relaxation of the muscles may break this cycle, too, [involving the sympathetic outflow to targets in skeletal muscle, e.g. blood vessels or other targets, or visceral targets and feedback via small-diameter afferents and spinal cord] through diminution of proprioceptor discharge into the cord….

What is stated here in one of the first papers by Korr was repeatedly formulated by him in the subsequent 30 years (see, for example, Korr 1978). Korr and co-workers developed their own methods to record the electrical skin response (dependent on the activity in sudomotor neurons [Thomas & Korr 1951, 1957, Thomas et al. 1958]), and the blood flow through skin (dependent on activity in cutaneous vasomotor neurons [Wright et al. 1960, Wright & Korr 1965]). Korr (1951) endeavored to develop methods to measure:

1. Blood flow through deep somatic tissues (which is dependent on activity in muscle vasoconstrictor neurons [and local changes]) using special thermocouples inserted into skeletal muscle, tendon, or ligaments;

2. Abnormalities in texture (hardness, resilience) in skeletal muscle and skin (trophic changes);

3. Chemical and metabolic changes in skeletal muscle;

4. Sensory changes such as spontaneous pain, hyperalgesia, and hyperexcitability in the tissues (skeletal muscle, skin, viscera); and

5. Changes in viscera using roentgenologic and other techniques.

Korr’s idea was to measure both systematically and quantitatively in humans (healthy subjects and patients) changes in the output channels of the spinal cord (to skeletal muscle, to autonomic targets in somatic tissues and viscera, to supraspinal centers [responsible for generating the sensations, including pain]) under controlled conditions in order to learn about the mechanisms underlying the osteopathic lesion and the facilitated segment. For Korr it was clear that both animals and more direct methods, such as electrophysiology, have to be used in research.

Korr hoped to work out why manual therapeutic interventions can be successful and how these interventions can be optimized to generate better and mechanism-based manual treatments. This was a modern research concept. Korr was fully aware that the main problems to be solved are (1) to work out the mechanism of the lesion process (preferentially in the skeletomotor system of the spine); (2) to learn about as to how this lesion process develops over time, i.e. to study its development under chronic conditions; and (3) how this lesion process is modulated (enhanced or attenuated) by supraspinal centers, in particular the telencephalon (Korr 1951).

Korr’s conclusions

Korr concluded from his research, using the measurements of the electrical skin response and cutaneous vasomotor response, that:

1. The activity in the sympathetic neurons to skin increased in patients with an osteopathic lesion;

2. This increase in activity in sympathetic neurons is restricted to a spinal segment and its neighboring segments;

3. This increased activity is a sign of increase of activity in all sympathetic outflow channels of these segments (i.e., also to the viscera and to the deep somatic tissues); and

4. This increased activity in sympathetic neurons indicates a general increase of excitability in these spinal segments (hence also of the somatomotor system, and of the systems mediating the afferent information to supraspinal centers) (Fig. 16.1).

Figure 16.1 The spinal cord as integrative organ.

1, Afferent inputs from skin, deep somatic tissues and viscera; 2, efferent outputs to skeletal muscles, autonomic effector cells (organs), supraspinal brain centers and other spinal segments; 3, descending systems from supraspinal centers (in brain stem and hypothalamus) to modulate processing of information from body tissues by neurons in the spinal gray; 4 (shaded box), ensemble of spinal neuronal programs (‘spinal reflex circuits’) processing transmission of activity in afferent neurons and systems projecting from supraspinal centers to the output systems of the spinal cord (see 2).

After Jänig (2005).

Korr believed that the main ‘motor’ or origin of the increased excitability is located in the (paraspinal) musculoskeletal system, and that it is maintained by multiple positive feedback circles (vicious circles) between skeletal muscle and spinal cord, as well as between viscera and spinal cord. Any neural impulse activity impinging on the facilitated segment was to contribute to this process, whether originating in the musculoskeletal system, the viscera, or supraspinal centers. By the same token he argued that therapeutic interventions at the deep somatic tissues (in particular of the spine), the skin, or the forebrain could interrupt this pathophysiological process.

Korr’s concept in the light of modern neurobiological research

Is Korr’s concept, which is at the heart of teaching, diagnosis, and treatment in osteopathic medicine (Lederman 2000), supported by modern neurobiological research? Here I will raise some critical questions in the light of such research conducted in the fields of pain and the autonomic nervous system. These critical remarks do not belittle what Korr has tried to achieve: Korr was modern in his time, as he tried to formulate testable scientific questions.

1. The research strategy recommended by Korr to explore the neural mechanisms of the osteopathic lesion and of the facilitated segment was absolutely correct. However, the actual design of the investigations was too much guided to justify the concept of the facilitated segment. Furthermore, the investigations conducted so far lack sound quantification and statistical comparisons, thereby weakening the conclusions drawn. This is of course also related to the technical limitations of the 1950s and 1960s that Korr was struggling with.

2. The mechanisms of the facilitated segment are explained by a general increase in the excitability of all systems in the spinal cord. I question whether these conclusions are sufficiently supported by the data that have been published.

3. In Chapter 2 of this book I stated that the sympathetic nervous system consists of many functional subsystems which are defined by the targets they innervate and regulate. In the periphery these systems consist of separate pre- and postganglionic channels that transmit the centrally generated impulse activity to the target cells. Every peripheral sympathetic pathway is connected to distinct neural circuits in the spinal cord, brain, and hypothalamus. Thus, I am skeptical that generalizations about the activity in sympathetic systems occurring under pathophysiological conditions such as Korr has made can be substantiated. From the increase in electrodermal skin responses generated during quasi-experimental interventions in humans, it cannot be inferred that the activity of sympathetic systems innervating skeletal muscle or viscera has also increased.

4. Korr’s generalization about sympathetic activity and his connecting this increase in sympathetic activity with the generation of diseases (e.g., in the viscera or deep somatic structures) and its decrease with the curative effects of manual therapy is questionable and unjustified, at least when based on the human or animal studies conducted so far. How important this concept was in Korr’s view can be seen from the title of his article ‘Sustained sympathicotonia as a factor of disease’ (Korr 1978).

5. The idea of vicious circles (positive feedback loops) involving skeletal muscle, viscera, and spinal cord is fascinating (see Chapter 7). However, this idea was not supported by the experimental data. It is still very much debated and remains an enigma, as we lack convincing experimental investigations on animal models and humans to support this concept (see below).

6. The integration between spinal circuits connected to the efferent motor systems (somatomotor system, sympathetic systems), the ascending tract neurons, and supraspinal control centers (see Fig. 16.1) is important in order to understand the mechanisms underlying the changes in the myotomes, viscera, and dermatomes. Korr knew this. He nonetheless assumed that the neural processes in the spinal cord (which include inhibitory and excitatory interneurons and output neurons) dictate the pathophysiological processes.

7. What is the experimental and clinical evidence (quantitative data) for osteopathic medicine to focus in teaching, clinical diagnosis, and treatment, primarily on the paraspinal skeletomotor system? In other words, why is the paraspinal skeletomotor system at the center of osteopathic medicine? What is functionally special with this system in relation to health and disease?

8. Korr showed that individual healthy subjects have specific (spatially relative invariant) patterns of electrodermal skin responses. He inferred that these patterns are enhanced during visceral diseases or myofascial diseases of the paraspinal apparatus (Korr et al. 1958, 1962). What is the quantitative evidence to support this conclusion? It has never been systematically studied in individual subjects that patterns of electrodermal skin responses present in healthy conditions remain invariant, but become stronger in intensity during disease. This does not question the findings of Beal and others that visceral diseases (e.g., of the heart, respiratory tract, different sections of the gastrointestinal tract, kidney, pelvic organs) are manifested in somatic tissues (deep somatic [myotomes, sklerotomes], skin [dermatomes]) in typical segmental patterns (Beal 1983, 1985, Beal & Dvorak 1984, Beal & Kleiber 1985, Beal & Morlock 1984, Hansen & Schliack 1962, Johnston et al. 1987, Schliack & Schiffter 1976).

9. The concept of the ‘facilitated segment’ and the ‘osteopathic lesion’ is interesting and fascinating. However, it needs better support based on quantitative measurements conducted in patients, healthy subjects, and animal models.

10. Research on human subjects (healthy controls, patients) is needed in which the sensory changes (including pain and discomfort) are compared quantitatively with the changes in skin (in the referred zones, dermatomes), in skeletal muscle (paraspinal and other; in the referred myotomes), and in the viscera (if possible).

Conclusion

Based on clinical observations and measurements in humans, Korr formulated the concept of the ‘osteopathic lesion’ (now somatic dysfunction) and the ‘facilitated segment’ (now spinal segmental dysfunction). He formulated testable scientific questions or hypotheses and tried to test them in human subjects, measuring changes in skin resistance and cutaneous blood flow. The attraction of Korr’s concept was that it included the somatic and autonomic motor components in explaining the mechanisms of functional deep somatic and visceral diseases. Thus, it was an integrative concept. Unfortunately, this concept was not developed further, and Korr’s investigations were not systematically followed. Thus, his ideas and conclusions were never challenged. Today we have the tools to do so.

The spinal cord as integrative organ

Organization of the spinal cord and its output systems

In Chapters 2 and 7 it was emphasized that the spinal cord is an integrative organ in its own right in the regulation of activity in spinal preganglionic neurons, and hence in the neural regulation of autonomic effector organs by spinal autonomic systems. The same principle applies to the regulation of activity in somatomotor neurons and hence of skeletal muscles. Thus the spinal cord contains a wealth of excitatory and inhibitory interneurons (segmental, propriospinal) which are involved in the following functions (Fig. 16.1):

1. Transmission and processing of afferent activity from the peripheral tissues (skin deep somatic tissues, viscera) to the output systems (somatomotor neurons, preganglionic neurons, ascending tract neurons projecting to brain stem, hypothalamus, and thalamus; 2 in Fig. 16.1).

2. Modulation of transmission of activity from premotor neurons located in the brain stem, hypothalamus, or cortex (for somatomotor neurons) to somatomotor neurons and to preganglionic neurons involved in the regulation of autonomic targets in somatic tissues or in the regulation of viscera (3 in Fig. 16.1). In this important function, activity in premotor neurons projecting to the spinal cord and activity in spinal circuits involving different groups of spinal excitatory and inhibitory interneurons are integrated (see pp. 28–35 [Spinal Cord] and Figs. 2.10 and 2.11 in Chapter 2).

3. Control of synaptic transmission from primary afferent neurons to second-order neurons in the dorsal horn by systems in the brain stem (this probably applies not only to transmission of nociceptive impulse activity, but most likely also to transmission of activity in all functional types of small-diameter afferent neurons [Aδ- and C-fibers] which monitor the mechanical, thermal, and metabolic states of the body tissues) (3 in Fig. 16.1).

4. Coordination of somatomotor systems, spinal autonomic systems, and systems controlling the synaptic transmission of afferent activity to second-order neurons.

The number of spinal interneurons (segmental and propriospinal) outnumber the number of spinal output neurons (motor neurons, preganglionic neurons, neurons projecting to supraspinal centers in brain stem, hypothalamus, and thalamus [ascending tract neurons]) by one order of magnitude (Polgar et al. 2004, Spike et al. 2003), indicating how important these interneurons are in the integrative activity of the spinal cord. Furthermore, in primates (and probably other mammalian species as well) the number of supraspinal neurons projecting to the spinal cord is probably much higher than the number of ascending tract neurons projecting to supraspinal centers, indicating how powerful the supraspinal control of spinal circuits is. This is also reflected in the fact that the volume of the spinal cord is about 2% of the volume of the brain in primates, but 35% in the rat (Swanson 1995). This argues that top-down control by the telencephalon is becoming quantitatively more important with the encephalization in evolution. It does not argue that the results we obtained in research on rodents do not apply to humans.

The dorsal horn of the spinal cord (and the trigeminal nucleus) can be divided functionally into three parts (Craig 2003a, 2008a, Dostrovsky & Craig 2006). This subdivision is somewhat speculative and not generally accepted. However, it helps to distinguish integrative aspects of interoception³ (pain in the three body domains, thermal sensations, other sensations of the skin [e.g., itch, sensual touch], sensations of the deep somatic tissues, visceral sensations, etc.), of exteroception (pressure, touch, vibration), and of regulation of somatomotor neurons and spinal preganglionic neurons:

1. The neurons in the superficial laminae I and II of the dorsal horn preferentially serve interoception of the body, and probably are also involved in autonomic reflexes. The ascending tract neurons in lamina I transmit impulse activity in afferent neurons with small-diameter (Aδ- and C-) fibers (from nociceptors, thermoreceptors, chemoreceptors in the skin; from mechanoreceptors and chemoreceptors in deep somatic tissues [skeletal muscle, joints, fascia] or viscera). These ascending tract neurons are specialized or relatively specialized with respect to the different types of afferent input (at least for the skin). Some of these lamina 1 tract neurons are convergent (wide dynamic range) neurons. Lamina I tract neurons project mainly to the posterior part of the ventromedial nucleus of the thalamus (VMpo), which in turn projects to the dorsal posterior insular cortex (dpINS). They also project to various nuclei in the brain stem and hypothalamus, and to the medial thalamus. The VMpo is developed in primates, particularly in humans, and appears to be either absent or rudimentary in other species, such as rats (Craig 2003a, 2004, Craig & Blomquist 2002). In the VMpo and the dpINS the body tissues are topographically represented. The dpINS is the interoceptive cortex (sometimes also called ‘limbic sensory cortex’) according to Craig (Craig 2002, 2003b, c, 2008b).

2. Lamina II (substantia gelatinosa Rolandi) contains only interneurons and propriospinal neurons, but no ascending tract neurons. This lamina is preferentially specialized for processing information in small-diameter afferents from the skin.

3. Laminae III and IV of the dorsal horn, together with the dorsal column–medial lemniscal system, serve exteroception and proprioception.

4. Most ascending tract neurons (and interneurons) in the deep dorsal horn (lamina V, VI, VII, X) can be activated by afferent neurons with Aβ-fibers as well as afferent neurons with small-diameter (Aδ- and C-) fibers (which include nociceptive afferents). They are convergent (‘wide dynamic range’) neurons which have large receptive fields and receive convergent afferent inputs from the three body domains. Their synaptic activation by stimulation of afferent neurons is mostly not monosynaptic and not modality specific. Ascending tract neurons in these laminae project to special nuclei in the thalamus that project to the somatomotor cortex. These tract neurons (and therefore also the interneurons in the spinal laminae of the deep dorsal horn) serve motor control (somatomotor and probably autonomic motor control); they are probably not involved in pain sensations or other interoceptive sensations (Craig 2006, 2008a, Craig & Zhang 2006). However, this subject is controversally discussed (Craig & Blomqvist 2002, Willis et al 2002, Willis & Coggeshall 2004).

These data and neurophysiological studies of spinal autonomic systems (see Chapter 2 in this book and Chapters 4 and 9 in Jänig 2006) strongly argue that the spinal cord contains the neural machineries that could explain the reciprocal relations between the three body domains (skin, deep somatic tissues, viscera). Thus they could explain:

1. Why functional diseases or dysfunctional states of viscera or deep somatic structures are expressed in changes to the corresponding dermatomes and myotomes;

2. Why manual and other interventions in one body domain (e.g., skin or paraspinal musculoskeletal system) could have beneficial effects on the corresponding diseased body tissues; and

3. Why supraspinal centers controlling the spinal circuits are important in interactions between the different body tissues.

Functional plastic changes of dorsal horn neurons in the spinal cord

Inflammation of peripheral tissues leads to sensitization of nociceptive primary afferent neurons (Fig. 16.2). This is reflected in the following changes of the nociceptive afferent neurons: development of ongoing (spontaneous) activity; decreased activation threshold and larger responses upon mechanical or thermal stimulation; and recruitment of mechanoinsensitive (silent) afferent neurons with unmyelinated axons. The cellular and subcellular (molecular) mechanisms of this sensitization are partially known, at least for the acute phase of sensitization (Hucho & Levine 2007, Julius & McCleskey 2006, Meyer et al. 2006, Ringkamp & Meyer 2009, Woolf & Ma 2007). However, it is debated whether the mechanisms of sensitization are the same in the chronic stage.