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137

C h a p t e r o u t l i n e

C H A P T E RC H A P TT E R

Introduction, 138

The definition of pain, 138

Types of pain, 139

Nociceptive pain, 139

Neuropathic pain, 140

Psychogenic pain, 140

Pain terminology, 140

The physiology of pain, 141

Nociceptors, 142

Spinothalamic tract neurons, 144

Thalamocortical neurons, 144

Cortical representation of pain, 144

Neuromodulation of pain, 146

Clinical manifestations of pain, 146

Evaluation and treatment, 146

Pathophysiology of pain, 148

Peripheral neuropathic pain, 148

Paediatrics and pain, 149

Central pain syndromes, 151

Ageing and pain, 151

Pain Mark Plenderleith

K e y t e r m s acute pain, 140 affective-motivational aspect, 138 allodynia, 141 analgesia, 139 anterior cingulate cortex, 144 beta-endorphin, 145 burning pain, 143 central pain syndromes, 151 central sensitisation, 151 chronic pain, 140 complex regional pain syndromes

(CRPSs), 150 endorphins, 145 encephalin, 145 fast-sharp pain, 143 high-threshold mechanoreceptors,

143 hyperalgesia, 141 interoceptive cortex, 144 mononeuropathy, 148 neuromodulators, 146 neuropathic pain, 140 nociceptive pain, 139 nociceptors, 142 opioid receptors, 145 pain threshold, 146 pain tolerance, 146 painful diabetic neuropathy, 150 peripheral neuropathic pain, 148 polyneuropathy, 150 polymodal nociceptors, 143 postherpetic neuralgia, 150 psychogenic pain, 140 referred pain, 140 sensory-discriminative aspect, 138 sharp pain, 143 slow-burning pain, 143 spinothalamic tract, 144 thalamocortical neurons, 144

7 C H A P T E R

138 PART 2 ALTERATIONS TO REGULATION AND CONTROL

Introduction Of all the sensations that arise from the human body, pain is one of the most clinically important. It is the sensation of pain that often motivates people to seek medical help as a result of a traumatic injury or a progressive disease,1 and it is often a consequence of surgical interventions used to treat injuries or disease. Pain is also clinically important as it encourages patients to adopt behaviours that enhance healing (such as limb immobilisation following a fracture).

Pain also has a very important physiological role, as it acts as the conditioning stimulus that teaches us to avoid environmental stimuli that cause harm. As children, we learn not to touch sharp objects because it hurts, and even as adults this sensation helps us to adapt to new or unusual environments. For example, as a postgraduate student in England I remember staring in disbelief as a visiting scientist from Australia (wearing only shorts) walked into a bush of head-high stinging nettles to retrieve a Frisbee. Never having been exposed to the leaves of this particular plant, he had no idea of the effect that they have on exposed skin — until he emerged screaming in agony from the bushes that many of us had learned as children cause intense pain.

In this chapter we consider the physiological basis of pain and then explore some of the clinical consequences of this very important sensation.

The definition of pain Pain is a complex and highly subjective sensation that is affected by a large number of variables and consequently can be difficult to describe. In 1979 the International Association for the Society of Pain (IASP) defined pain is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage’.2 Although this definition is a little cryptic it does highlight some of the key concepts related to pain. So to help you understand some of the most important elements of this complex sensation, let us have a closer look at this definition.

The first thing that the IASP definition reminds us of is that pain is unpleasant. Whether the pain is caused by touching something hot or is the result of a surgical procedure or the growth of a tumour, the experience is likely to be a negative one. Although the intensity of the experience may vary from individual to individual and has been shown to be influenced by sex, race, age, culture, beliefs, previous experience, fear and anxiety,3–5 pain is invariably unpleasant and therefore is something we avoid or try to minimise.

The second concept that emerges from the definition is that pain is a sensory experience. In some respects pain is no different from other senses such as hearing, taste or vision. Just as we can look up into the sky at night and define the position of a star, describe how bright it is and even attribute to it a colour, so we can identify the site and intensity of a painful stimulus applied to our bodies.

Humans are, in general, very good at identifying the site of an injury that causes pain and can readily distinguish between stimuli of different intensities and indeed modalities. A pin prick applied to the anterior surface of the arm is thus easily distinguishable from a drop of acid applied to the wrist, not just by location but by the sharp quality of the former and the burning sensation produced by the latter. Indeed, psychophysical experiments using carefully controlled thermal stimuli have shown that humans can distinguish between two high-intensity thermal stimuli that differ by as little as 0.1°C.6 This ability to locate a painful stimulus and describe both its intensity and its quality is referred to as the sensory-discriminative aspect of pain.

The definition then goes on to point out that pain is much more than a sensation — it is also an emotional experience. Because it is unpleasant (i.e. it is a negative experience) it also elicits an emotional response in that it produces changes in both mental (affective) state and behaviour (motivation). Individuals exposed to a painful stimulus become anxious, tense, distressed or scared and, if the pain is ongoing, they may become depressed, develop a feeling of hopelessness and, ultimately, may even consider suicide. In addition, individuals are motivated to remove themselves from the source of the pain, avoid similar environments in the future and/or adopt behaviours that enhance healing. The degree to which these responses manifest themselves depends on a number of factors, including the intensity of the pain, its duration, the individual’s past experience and the availability of treatment. However, it is the emotional aspect of pain that predominates in severe and/or ongoing pain. The changes in mental state and behaviour that are part of the emotional component of pain are collectively referred to as the affective-motivational aspect of pain.

The next part of the definition states that pain is caused by ‘actual or potential tissue damage’. This serves to remind us of two very important components about pain. The first is that it is normally produced by stimuli that are sufficiently intense to cause peripheral tissue damage (i.e. damage to peripheral tissues such as skin, muscle or visceral organs). So cutting the skin, impaired blood flow to the heart or damage to the wall of the digestive tract all cause pain because they result in ‘actual’ tissue damage. In other words the stimulus is of sufficiently high intensity for the integrity of the tissue to be compromised and we become aware of this because it results in pain. The second point that is implied by this part of the definition is that pain can also result from stimuli that have the ‘potential’ to cause tissue damage. Therefore, touching something hot or stepping on a sharp object may cause pain, but little or no tissue damage, because the rapid withdrawal reflex removes your limb from the pain source (see Chapter 6). This is possible because the threshold for pain in some tissues is lower than the threshold for tissue damage, so behavioural modifications allow us to remove ourselves from the source of the stimulus or adopt behaviours that minimise tissue damage. Therefore, one important function of pain is to advise us of the presence of stimuli

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that could cause us harm and thereby provide us with the opportunity to prevent it happening (or reduce its impact).

The last part of the definition is probably the most cryptic as it is not immediately obvious what is meant by the phrase ‘or described in terms of such damage’. We know that pain is usually caused by stimuli that cause tissue damage (or have the potential to), but this part of the definition implies that you can experience pain that feels like it is caused by tissue damage without there being any peripheral tissue damage. Although this sounds counterintuitive, this is exactly the point. People can experience pain in parts of their body that do not exhibit any sign of disease or trauma. For example, a patient may complain of a severe burning pain in their left foot without the limb having been exposed to a heat source or showing any signs of peripheral tissue damage. The pain feels like it was caused by a burn injury, but there is no evidence of any peripheral tissue damage. In the absence of any physical evidence, in the past individuals experiencing this type of pain were sometimes considered hysterical or delusional and the pain was attributed to a psychological disorder. We now know that most such types of pain are the result of damage to the parts of the peripheral and central nervous systems responsible for sensations that arise from the affected tissue. Thus, although there is no peripheral tissue damage, the pain feels like it is caused by such damage.

One of the factors that can contribute to the variable nature of the pain experienced is that the pain can be modified. In other words, the intensity of the sensation can be affected by behaviour, cognitive factors and clinical intervention. For example, in response to minor burns or cuts many people immediately rub the site of the injury. We do this because we have learned that this reduces the intensity of the pain (i.e. produces analgesia). Furthermore, soldiers in combat situations may suffer quite severe injuries but experience comparatively little pain because of the stress associated with the life-threatening

situation. This type of pain modification is not limited to the battlefield, as anyone who has watched any Australian or New Zealand football code can attest. Analgesia can occur in trance-like states associated with certain religious and cultural rituals, and in the clinical environment analgesia can be produced by pharmacological agents, such as opioids, but also through other avenues, such as transcutaneous electrical nerve stimulation, acupuncture and cognitive behaviour modification.

Collectively, pain can be considered a negative multi- dimensional experience that is typically associated with peripheral tissue damage but in some pathological circ- um stances may exist in the absence of tissue damage. As a subjective experience, pain is highly labile and may be modified by cultural, situational and psychological as well as clinical interventions.

Just how important pain is to the wellbeing of humans is perhaps best illustrated by considering the rather serious consequences of being unable to feel pain. Individuals born with a congenital insensitivity to pain suffer horrendous injuries because they are unaware of the damage they are doing to their bodies when, for example, they sit too close to a fire or bite into their tongue while eating (see Figure 7-1).7,8 They do not make the regular adjustments to their posture necessary to avoid damaging joints and can be completely oblivious to internal damage caused by disease. Not surprisingly, these types of injuries often become infected, are slow to heal and can be life- threatening.

Types of pain Most common types of pain fall into one of three categories that vary in terms of their aetiology (or cause), duration and ease of treatment.

Nociceptive pain Nociceptive pain is the most common type of pain and its defining characteristic is that it is produced by

A B

FIGURE 7-1

Congenital insensitivity to pain. Photographs illustrating tissue damage in a 9-month-old boy with congenital insensitivity to pain. A Damage to the left thumb and index

finger caused by biting. B Severe mutilation of the tongue.

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140 PART 2 ALTERATIONS TO REGULATION AND CONTROL

nociceptive stimuli, which cause or have the potential to cause peripheral tissue damage. Nociceptive pain can be subdivided into two subtypes: • External damage. Pain due to external damage is the

most common form of nociceptive pain and you are likely to have experienced it. As the name implies, this type of pain usually involves trauma to the skin but may extend to the underlying tissues. It is relatively mild and has a comparatively short time course, lasting a few seconds to a few days. Treatment of this type of pain usually involves simple interventions that assist the healing process of the affected tissues. Moreover, pain relief is relatively easy to achieve through the use of milder forms of analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs).

• Internal damage. Pain due to internal damage is less common and usually more severe than that associated with external damage. It has numerous causes. One of the principal causes is severe trauma, for instance due to bone fractures, surgery or childbirth. This type of pain is also associated with disease. In fact, pain is a symptom of virtually every disease (e.g. cancer, arthritis) at some point during the disease progression. The duration is usually quite a bit longer than that following external injury and typically is in the order of a few days to weeks. Treatment involves removing the cause of the tissue damage, but interim management of pain can be achieved with more powerful opioid analgesics.

Neuropathic pain As the term implies, neuropathic pain is caused by injury or disease of the nervous system rather than a peripheral tissue.9 Fortunately, this type of pain is less common than nociceptive pain. Neuropathic pain is usually more severe and has a time course that can last from a few months to many years — and sometimes the rest of a person’s life. Because of the complex aetiology and the lack of knowledge of the underlying mechanisms, treatment is challenging. In some cases pharmacological interventions, particularly when used in combination, produce positive outcomes for patients. However, for others, pain relief is less satisfactory and specialised ongoing therapies are required in an effort to alleviate the effects of neuropathic pain. Forms of neuropathic pain are dealt with in more detail later in this chapter.

Psychogenic pain It is well recognised that some people report pain that may be severe and persistent but for which there appears to be no underlying pathology. The pain experienced by these patients (typically headaches, abdominal pain, back pain) is indistinguishable from that experienced by people with identifiable injuries or disease. Such pain can be debilitating and consequently interferes with their ability to function normally. In the absence of any physical explanation for the symptoms, despite exhaustive clinical examination and testing, the assumption is made that the pain is the result

of a psychological disorder, so it is termed psychogenic pain. It is very likely that some pain of neuropathic origin was at one time incorrectly diagnosed as psychogenic pain due to similarities in symptoms and the absence of any visible cause. However, due to improvements in diagnosis and more sophisticated medical imaging, diagnosis of psychogenic pain is less common.10

FOCUS ON LEARNING

1 Describe what is meant by the sensory-discriminative aspect of pain.

2 Describe what is meant by the affective-motivational aspect of pain.

3 Differentiate between nociceptive, neuropathic and psychogenic pain.

4 Describe some of the ways in which pain can facilitate the healing process.

Pain terminology Whereas some types of pain have a relatively short time course, others last a very long time indeed. In order to discriminate between these types of pain, the terms acute pain and chronic pain are used. Acute pain refers to any pain that lasts less than 3 months. In contrast, chronic pain is any pain that lasts longer than 3 months. The timelines outlined in the previous section suggest that most neuropathic pain is chronic pain, and although this is often the case, the two terms should not be used interchangeably. The terms acute and chronic refer exclusively to the time course of the pain, irrespective of aetiology. For instance, neuropathic pain that resolves within 3 months is considered acute, while cancer-related nociceptive pain that persists for more than 3 months is chronic. Approximately one-fifth of Australians suffer from chronic pain11 and are about five times more likely to use healthcare services than those without chronic pain.12 Therefore, patients with chronic pain are a concern in the healthcare industry and you are likely to encounter them in all areas of the health sector.

Another important aspect of pain is the location of the pain. Typically, neuropathic pain feels like it is coming from the part of the body that the affected nerve innervates. For example, a compression injury of branches of the sciatic nerve (shown in Figure 6-15) caused by damage to a vertebral disc can result in pain in the leg or foot. Interestingly, this disconnection between injury site and pain location is not restricted to neuropathic pain, but also occurs in some forms of nociceptive pain. For example, the first symptom of appendicitis is usually tenderness in the midline abdominal region, despite the inflamed appendix being located in the right lower quadrant (see Chapter 27). Similarly, one of the classical signs of myocardial infarction (see Chapter 23) is a shooting pain referred to the left shoulder or arm, when the tissue damage is actually occurring in the heart (see Figure 7-2). We refer to this type of pain as referred pain.

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Following injury the affected tissue becomes very sensitive to subsequent stimuli. Thus, we tend to protect a bruised heel or burnt hand because any additional stimulation greatly enhances the pain. The increased sensitivity that follows peripheral tissue damage can be attributed to two factors: there can be an amplified neural response to any subsequent painful stimulus and/or a decrease in the threshold such that previously non-painful stimuli now cause pain. To accommodate these two different characteristics we use the term hyperalgesia to describe the situation where the original tissue damage augments the pain produced by subsequent high-intensity (damaging) stimuli. The term allodynia refers to a reduction in the threshold such that pain is now produced by low-intensity (non-damaging) stimuli. (See Box 7-1 for key pain terminology.) These changes in sensitivity occur in nociceptive pain and many forms of neuropathic pain. For example, individuals with trigeminal neuralgia (an alteration to cranial nerve V causing episodes of excruciating pain to the face) rarely wear high collars or scarves because of mechanical allodynia, where even the gentle touch of such clothing can elicit excruciating pain referred to the face.13

The physiology of pain Since pain is the conscious perception of a stimulus that causes tissue damage, this means that the presence of the stimulus has to be detected in the tissue and then information about the tissue damage relayed to the cerebral cortex, where it is consciously perceived as pain. In order to enable this, small patches of each peripheral tissue (skin, muscle and viscera) are connected to regions of the cerebral cortex by a three-neuronal pain pathway (see Figure 7-3). The first-order neuron in this path- way carries the information from the periphery to the spinal cord, where it synapses with the second-order neuron. This second-order neuron relays the information to a number of sites in the brain. Some of the brain sites are involved in the autonomic nervous system reflex responses to injury (such as increases in cardiac output or ventilation rate). However, conscious perception of tissue

Heart Liver

Small intestine

Kidney

Ureter

A B

Lung and diaphragm

Pancreas Stomach

Ovary Kidney

Colon

Bladder

Liver

Appendix

A B

FIGURE 7-2

Visceral referred pain. Examples of some of the typical sites of referred pain from visceral structures on A the anterior and B the posterior surface of the body. (See also Box 7-2 later in this chapter.)

Acute pain Pain that lasts less than 3 months. Allodynia Pain due to a stimulus that does not normally provoke pain. Analgesia Absence of pain in response to a stimulus that would normally be painful. Chronic pain Pain that lasts longer than 3 months. Hyperalgesia An increased response to a stimulus that is normally painful. Referred pain Pain perceived as occurring in a region of the body topographically distinct from the region in which the

actual source of pain is located.

BOX 7-1 Key pain terminology

FIGURE 7-3

Basic arrangement of the pain pathway. Schematic diagram showing that the pain pathway consists of three neurons, which connect peripheral tissues (skin, muscle and viscera) with the cerebral cortex. Large numbers of these three neuronal pathways are arranged in parallel to ensure that most tissues in the body are connected to the cortex.

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142 PART 2 ALTERATIONS TO REGULATION AND CONTROL

damage is transmitted from the thalamus via the third- order neuron, which relays the information to the cerebral cortex. It is here that the individual becomes aware of the pain. Large numbers of these three-neuronal relays are arranged in parallel to ensure that most tissues in the body are connected to the cerebral cortex. The structure and function of each of these three classes of neuron are considered in more detail in the following section.

Nociceptors Nociceptors are the first-order neurons in the pain path way. They are a subpopulation of the primary sensory neurons that collectively are responsible for the detection of all sensations, such as touch, temperature, muscle length and joint position (see Chapter 6). Like other primary sensory neurons, they have a cell body located in the posterior root ganglia, just outside the spinal cord, and an axon that runs from the peripheral tissue through a peripheral nerve and terminates within the superficial layers of the posterior horn of the spinal cord (see Figure 7-4).

The important thing about nociceptors is that they are selectively activated by high-intensity stimuli that have the potential to cause tissue damage. Thus, they are not activated by low-intensity (innocuous) stimuli, and only respond when the stimulus is of sufficient intensity to threaten the integrity of the tissue they innervate.

In addition, tissue damage leads to the release of substances that produce pain. These substances are intricately involved in the inflammation process (see Chapter 13 for more detail) and often cause a cascade of inflammatory events, such as vasodilation, local swelling and stimulation of nociceptors. The most recognised substances are bradykinin, histamine and prostaglandin. Some substances are released by cells that migrate to the injured site, such as mast cells and white blood cells, while other substances are released by the tissues themselves. These substances flood the injured site during the inflammatory process and have been referred to as an ‘inflammatory soup’ (see Figure 7-5). Collectively, they stimulate nociceptors, which transmit the pain signals to

FIGURE 7-4

Detailed arrangement of the pain pathway. The relationship between nociceptors (red), spinothalamic tract neurons (blue) and thalamocortical neurons (green) as they course through the peripheral and central nervous systems.

FIGURE 7-5

Tissue damage leading to inflammation and stimulation of nociceptors. In this example, tissue damage has occurred to the skin causing the release of a ‘soup’ of substances, namely bradykinin, serotonin, potassium and prostaglandin, which stimulate nociceptors. Mast cells degranulate (release the contents of) histamine when triggered by tissue damage, which stimulates the nerve ending but also causes the blood vessels to allow fluid to leak into the extracellular space, causing swelling and more pain stimulation.

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the brain and then the individual becomes aware of the injured tissue.

Not surprisingly, nociceptors have been identified in virtually every peripheral tissue from which we experience pain. However, a lot more is known about the properties of the nociceptors responsible for sensations that arise from the skin than from other structures. Therefore, we begin by examining the properties of these cutaneous nociceptors before considering what is known about the neurons responsible for detecting tissue damage in deeper tissues such as muscle and viscera.

Cutaneous nociceptors It is well established that there are two distinct pain sensations — sharp pain and burning pain — that differ in their timing and quality. These can be clearly demonstrated by a mechanical injury such as that produced by a paper cut or pin-prick. Very shortly after a mechanical injury we experience a pain that has a ‘sharp’ quality. A few seconds later we experience a second pain sensation that is usually described as ‘burning’. The burning pain can also be elicited by exposure to high temperatures and by the application of pain-producing chemicals such as acid. Underlying these two sensations are two classes of nociceptor in the skin that are quite distinct in structural and functional properties: high-threshold mechanoreceptors and polymodal noci- ceptors (see Table 7-1).

High threshold mechanoreceptors Structurally, high threshold mechanoreceptors have small diameter myelinated axons in which action potentials travel along their length at about 5–15 m/sec. The axons terminate within the dermis of the skin as simple ‘free nerve endings’ with none of the specialised structures associated with low threshold mechanoreceptors (such as touch receptors).

As the name suggests, high threshold mechanoreceptors are activated by high intensity mechanical stimuli such as a pin-prick, cutting or pinching the skin. They are completely unresponsive to low-threshold stimuli (touch, vibration, warmth) or to painful thermal or chemical stimuli.

Clearly this class of cutaneous nociceptor is very well- suited to detecting mechanical injury of the skin as they are activated only by mechanical stimuli at intensities high enough to cause damage. In addition, because these neurons have myelinated axons they are able to relay information about a mechanical injury to the spinal cord rapidly. For these reasons, high threshold mechanoreceptors are responsible for detecting the fast-sharp pain that follows a mechanical injury of the skin.

Polymodal nociceptors Like high threshold mechanoreceptors, cutaneous polymodal nociceptors have free nerve endings in the dermis, with some projecting into the epidermis. Therefore, they are well positioned to detect stimuli affecting the skin. They have small-diameter axons but no myelin sheath and consequently action potentials travel along these

unmyelinated axons relatively slowly (0.5–2.5 m/sec) compared to high-threshold mechanoreceptors.

As their name suggests, this class of nociceptors respond to multiple modalities of high intensity stimuli. They respond to the same high intensity mechanical stimuli that activate high-threshold mechanoreceptors but in addition are activated by high temperatures (above 45°C) and a range of chemicals (such as acid). This is important, because these intense thermal and chemical stimuli will cause pain when exposed to the skin. Thus, this class of nociceptor is truly polymodal in that they respond to mechanical, thermal and chemical stimuli of sufficient intensity to cause damage to the skin. As polymodal nociceptors are activated by high intensity mechanical stimuli, but have unmyelinated axons and hence a slow conduction velocity, they are responsible for the slow- burning pain that follows mechanical injury of the skin. In addition, the burning sensation that is characteristic of heat or chemical injury to the skin is relayed by these receptors.

A mechanical injury such as a cut will, of course, activate both high threshold mechanoreceptors and poly modal nociceptors in the skin at exactly the same time. However, because action potentials travel along myelinated axons much more quickly than along unmye- linated axons, the information carried by the high threshold mechanoreceptors reaches the spinal cord before that carried by the polymodal nociceptors. Because this time difference is maintained all the way through to the cerebral cortex the first sensation we perceive is mediated by the high threshold mechanoreceptors and has a sharp quality (fast-sharp pain) and this is followed a couple of seconds later by a burning sensation because of the activity of polymodal nociceptors (slow-burning pain).

Musculoskeletal and visceral nociceptors Studies of nociceptors in deeper tissues (muscles, joints and visceral organs) suggest that the vast majority have unmyelinated axons and therefore relatively slow conduction

TABLE 7-1 Comparison of the structural and functional properties of cutaneous nociceptors

HIGH-THRESHOLD POLYMODAL FEATURE MECHANORECEPTORS NOCICEPTORS

Axon diameter Small Small Myelin sheath Yes No

Conduction velocity 5–15 m/sec 0.5–2.5 m/sec Activated by low- threshold stimulus

No No

Activated by mechanical injury

Yes Yes

Activated by thermal injury

No Yes

Activated by damaging chemicals

No Yes

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velocities.14–16 Some of these are activated by high-intensity mechanical stimuli as well as a variety of pain-producing chemicals. Although the temperature sensitivity of these neurons can be difficult to test, many of them respond to high temperatures, suggesting that they are like polymodal nociceptors. As these neurons are not activated by low- intensity stimuli they are very well-suited at detecting the twisting of joints, the distension of visceral organs and ischaemia, which often causes pain in deeper tissues.

A new class of nociceptor has been identified in joints, muscle and visceral organs that is completely insensitive to stimulation in normal healthy tissue. These nociceptors cannot be activated by either low intensity or high intensity stimulation and are called silent (or ‘sleeping’) nociceptors.16 However, if the peripheral tissue these neurons innervate becomes inflamed, they are activated and may even begin to respond to relatively low-threshold stimuli — that is, stimuli that would not cause pain in healthy tissue. Interestingly, these neurons do not appear to have any physiological role but instead are responsible for the sometimes debilitating pain that is often associated with tissues that become inflamed because of damage or disease.

in the thalamus. The thalamus is a large, oval-shaped structure located deep within the forebrain underneath the cerebral hemispheres and lateral to the third ventricle (see Figure 7-4). It is a major component of the diencephalon, and receives information from all the senses (except smell) and passes this on to the cerebral cortex. The thalamus is made up of a large number of nuclei, named according to their anatomical position. Spinothalamic tract neurons terminate in two structurally distinct regions of the thalamus. Some neurons terminate in a group of nuclei in the posterolateral (back and to the side location) part of the thalamus, while another population synapse in the medial (towards the midline) region (see Figure 7-4). These two different termination sites form the basis for projections from the thalamus to the cerebral cortex.

Thalamocortical neurons The third-order neurons of the pain pathway collect the information relayed to the thalamus by spinothalamic tract neurons and relay this to the cerebral cortex, and so are referred to as thalamocortical neurons. As there are two thalamic sites that receive information about peripheral tissue damage from the spinothalamic tract, there are two distinct populations of thalamocortical neurons: • Thalamocortical neurons with their cell bodies in

the posterolateral parts of the thalamus are activated by high-intensity stimulation of small, well-defined regions in the periphery and relay this information in a highly ordered fashion to the somatosensory cortex of the parietal lobe and the adjacent insular cortex. The insula is the lobe of the cerebral cortex hidden behind the parietal and temporal lobes, and the region where these lateral thalamocortical neurons terminate is referred to as the interoceptive cortex (see Figure 7-4) as it receives sensory information about the physiological condition of the whole body.

• Thalamocortical neurons that are located in the medial thalamus tend to be activated by painful stimulation of large areas of the body — for instance, a whole limb — and relay this information to the anterior cingulate cortex of the frontal lobe (see Figure 7-4).

Cortical representation of pain There are three known cortical regions that are responsible for the perception of pain: the lateral pain pathway that terminates in the parietal and insular lobes, and a medial pain pathway that terminates in the frontal lobe. Functional brain imaging and analyses of patients with damage to these different cortical areas suggest that they are responsible for different aspects of the pain experience.

Brain imaging analyses of both somatosensory and interoreceptive cortices have revealed that they are activated by painful peripheral stimuli.17 In addition, electrical stimulation of the interoreceptive cortex in conscious humans has shown that the pain is located in

FOCUS ON LEARNING

1 Discuss why a paper cut causes two sensations that have different qualities and delays.

2 Describe the anatomy of nociceptor cell bodies and axon terminals.

3 Provide an explanation of the type of nociceptor responsible for the pain associated with myocardial infarction (heart attack).

Spinothalamic tract neurons The nociceptors that relay action potentials intersect with the spinal cord. The ascending pathway connects the spinal cord with the thalamus and consequently is referred to as the spinothalamic tract (refer to Figure 6-19). Spinothalamic tract neurons are second-order neurons in the pain pathway and they receive information about peripheral tissue damage from nociceptors and relay it to the thalamus.

Spinothalamic tract neurons have their cell bodies located in the superficial layers of the grey matter of the posterior horn of the spinal cord (see Figure 7-4). Therefore, they are well positioned to receive the inputs from the nociceptors that terminate there. The axons of spinothalamic tract neurons cross the midline of the spinal cord underneath the central canal and then ascend along the length of the spinal cord in the white matter on the opposite side. The axons of spinothalamic tract neurons from different parts of the body appear to run together in a white matter tract (the funiculus, which translates as ‘slender cord’), which is located between the anterior funiculus and lateral funiculus and is known as the anterolateral funiculus (see Figure 7-4).

The axons of spinothalamic tract neurons project out of the spinal cord, through the brainstem and terminate

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well-defined peripheral tissues.18 This is supported by the observation that damage to this part of the cortex interferes with pain perception.19 These observations have led to the suggestion that the lateral pain pathway is responsible for the sensory-discriminative aspect of pain (i.e. the position, intensity and modality of the tissue damage).

Analysis of the anterior cingulate cortex with functional

imaging has revealed that it is activated by peripheral tissue damage and that these responses can be alleviated by hypnosis.20,21 Furthermore, patients who have damage in this region can still feel pain but are less troubled by it.22 Therefore, it is believed that the medial pain pathway is involved in the affective-motivational aspect of pain.

Interneuron

Pain receptors

(afferent pathway)

To thalamusInterneuron

Excitatory impulse (afferent pathway)

Impulse from brain (efferent pathway)

Dorsal root ganglion

Narcotic

Opiate receptor

Pain transmission blocked by release of endorphins

To th

ala mu

FIGURE 7-6

Descending pathway and endorphin release. Endorphin receptors are located close to the known pain receptors in the peripheral tissues and pain pathways in the spinal cord.

Although the origin of cutaneous and musculoskeletal pain is usually fairly well-defined (that is, we can determine the origin of the pain fairly well), visceral pain can be a little more difficult to localise. For example, pain from the heart is often referred to the left shoulder and arm. It is thought that when many nociceptors from different peripheral tissues merge onto the same spinothalamic tract neurons, the pain will be referred. So, a population of spinothalamic tract neurons may receive input from nociceptors in the left arm as well as the heart. Typically, they are activated by injury of the skin or muscles of the left arm, and the cerebral cortex associates activity in these neurons with arm pain. However, the cerebral cortex cannot distinguish between this and activation of the same neurons by nociceptors in the heart, so the angina pain is referred to the left arm. The exact reason for this is not known.

Endorphins (endogenous opioids produced by the body) inhibit transmission of pain impulses in the spinal cord and brain by binding to opioid receptors. These are receptors in the central nervous system that block pain transmission. You may be familiar with the term endorphins as they are released during exercise and produce the ‘runner’s high’ that gives the exercising individual a sense of euphoria, despite being physically drained and experiencing pain. It is thought that endorphins attach to the limbic and prefrontal areas of the brain (involved in emotion), which alters the individual’s mood. Beta-endorphin is a potent substance, released from the hypothalamus and pituitary gland, which results in analgesic effects. It may also be responsible for general sensations of wellbeing. Encephalin, found in the neurons of the brain and spinal cord, is a weaker analgesic than other endorphins but is more potent and longer lasting than morphine.

All endorphins attach to opioid receptors on the cell membrane of the afferent neuron (see Figure 7-6) and inhibit the release of excitatory neurotransmitters. Opioid analgesics relieve pain by attaching to the opioid receptors and enhancing the natural endorphin response. Stress, excessive physical exertion, acupuncture, sexual intercourse and other factors increase the levels of circulating endorphins, serotonin, noradrenaline and other neurotransmitters, thereby raising the pain threshold.

BOX 7-2 Mechanisms of referred pain

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146 PART 2 ALTERATIONS TO REGULATION AND CONTROL

Neuromodulation of pain As well as the neural pathways, several substances are capable of altering the pain pathways. Collectively, these are referred to as neuromodulators. They are found in the pathways that control information about painful stimuli throughout the nervous system. Neuromodulators are substances, other than neurotransmitters, which are released by neurons and transmit signals to other neurons that change the activities of these neurons. It is thought that neuromodulators are released in response to tissue injury (such as prostaglandins, bradykinin) and chronic inflammatory changes (cytokines; see Chapter 12). Excitatory neuromodulators (ones that propagate the action potential that excites the neuron) include substances such as glutamate, substance P, somatostatin and vaso- active intestinal polypeptide. Inhibitory neuromodulators (ones that delay or stop nerve transmission) include gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (serotonin), noradrenaline and endorphins.

well as sweating, when experiencing pain, especially acute surgical pain. However, these clinical signs are not universal in all individuals who are experiencing pain. When there is damage to the internal organs, this can also result in activation of the sympathetic nervous system, causing an elevation in cardiovascular and respiratory responses.

Evaluation and treatment The evaluation of pain is often difficult. Nurses are usually the primary clinicians responsible for assessing a patient’s pain. Foremost in the evaluation of pain is to listen to, and believe, what the patient says about their level of pain. There is no single test that assesses an individual’s level of pain and, despite numerous measures to provide an objective measure of pain, the most useful is asking the patient to relate the location, type and duration of the pain, as well as any therapies previously used to effectively alleviate pain.

As well as receiving information from the patient about their pain, there are numerous pain measurement tools that the clinician can use to obtain more information about the patient’s pain (see Figure 7-7). These can be used to assess changes in the patient’s level of pain and response to therapies. In addition, facial pain scales can be used for individuals who may not be able to vocalise their feelings of pain or who cannot speak (see ‘Paediatrics and pain’ below).

The management of pain can be divided into pharmacological and non-pharmacological therapies, or a combination of both. The principal management aim should be to treat the cause of pain, if possible. Second, choose appropriate therapies that target the type of pain. For instance, opioids and NSAIDs target nociceptive pain. If using pharmacological agents, provide doses regularly and prevent pain from arising, such as postsurgical pain. The administration route also becomes important when deciding the severity of the pain. While originally developed for the management of cancer pain, the World Health Organization (WHO) analgesic ladder provides a simple scale for the determination of pharmacological agents in pain management (see Figure 7-8). The effect of different types of analgesic agents on pain pathways is illustrated in Figure 7-9.

If the pain is bilateral, then more effective relief can be produced by a midline myelotomy (see Figure 7-10). The objective of this procedure is to cut the axons of the spinothalamic tract neurons as they cross the midline underneath the central canal. A midline myelotomy is a complicated procedure as it usually requires a laminectomy to access the posterior surface of the spinal cord and special care to ensure that the lesion is made at the correct level in order to target the axons of the appropriate spinothalamic tract neurons. However, the advantage of the procedure is that it cuts the axons of the spinothalamic tract neurons crossing the midline from both sides of the spinal cord and so produces bilateral analgesia, which is particularly beneficial when the pain is of visceral origin. (See also Box 7-3.)

FOCUS ON LEARNING

1 Discuss why a cut in the right thalamus might interfere with the ability to feel pain on the left side of the body.

2 Outline which cortical sites are thought to be involved in the conscious perception of pain.

3 Describe how neuromodulators of pain alter pain signal transmission.

Clinical manifestations of pain Pain is complex and highly subjective, meaning that no two people are likely to experience the same level of pain for a given painful stimulus. Pain tolerance is the amount of time or the intensity of pain that an individual will endure before initiating overt pain responses. Pain tolerance varies greatly among individuals, as well as in the same individual over time, because of the body’s ability to respond differently to noxious stimuli. It is influenced by cultural perceptions, expectations, role behaviours, gender and physical and mental health.23 It generally decreases with repeated exposure to pain, fatigue, anger, boredom, apprehension and sleep deprivation; and may increase with increased alcohol consumption, medication, hypnosis, warmth, distracting activities and strong beliefs or faith.

The pain threshold is the lowest intensity at which a stimulus is perceived as pain and may be influenced by genetics.24 Intense pain at one location may increase the threshold in another location. For example, a person with severe pain in one knee is less likely to experience chronic back pain that is less intense. Therefore, an individual with many painful sites may report only the most painful one. Then, when the dominant pain is diminished, the individual identifies other painful areas.

While pain is a subjective sensation, it may result in changes in the level of autonomic nervous system activation. Patients often experience an increase in heart rate, blood pressure, ventilation, nausea and vomiting, as

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CHAPTER 7 PAIN 147

Pain intensity scale

No pain

Mild pain

Moderate pain

Severe pain

Worst possible

pain

Pain distress scale

None Annoying Uncomfortable Bad Dreadful Agonising, unbearable

0 1 2 3 4 5 6 7 8 9 10

0–10 numerical pain intensity scale

Simple descriptive pain distress scale

0 NO HURT

1 HURTS

LITTLE BIT

0 2 4 6 8 10

2 HURTS

LITTLE MORE

3 HURTS

EVEN MORE

4 HURTS

WHOLE LOT

5 HURTS WORST

FIGURE 7-7

Scales for rating the intensity of pain. The numerical and facial scales can be used by patients to self-rate their pain. A Pain intensity scale. B Pain distress scale. C Facial pain scale

for children. D Facial pain scale for adults, used in multiple languages.

Due to their well-characterised anatomical location, the axons of spinothalamic tract neurons are sometimes targeted in surgical approaches for the treatment of severe chronic pain in patients whose pain is inadequately controlled by analgesics.25,26 Because of the importance of these neurons in the onward transmission of the pain signal, cutting the axons should result in abolition of the pain.

In an anterolateral cordotomy (-otomy refers to surgical cutting) the objective is to cut the axons of the spinothalamic tract as they course through the anterolateral funiculus. At one time this involved exposing the lateral surface of the spinal cord with an operation called a laminectomy, so that the cordotomy could be performed under direct visual control. Today, it is performed percutaneously (through the skin) and involves the insertion of an electrode into the anterolateral funiculus of the upper cervical segments of the spinal cord, which is visualised using computed tomography (CT) scanning. The cut is made by heating the tip of the electrode. Anterolateral cordotomy is particularly useful when the pain is unilateral, as the lesion only affects the axons of the spinothalamic tract on one side of the body (see Figure 7-10A).

BOX 7-3 Surgical treatment of chronic pain

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148 PART 2 ALTERATIONS TO REGULATION AND CONTROL

Pathophysiology of pain So far we have considered pain from a physiological perspective and have identified it as both having a protective function (warning us about environments that can cause us harm) and acting as a stimulus to adopt behaviours that enhance healing. However, when the nervous system components that are responsible for detecting pain are themselves affected by injury or disease, the consequences can be severe and persistent neuropathic pain. It has been estimated that chronic pain affects about 3.2 million Aust ralians and that the total cost of chronic pain on the Australian economy is about $34.3 billion per year — that is, more than $10,000 per person with chronic pain.27 Healthcare costs are estimated to comprise 20% of these costs (about $7 billion per year), mainly due to inpatient, outpatient and out-of-hospital medical costs.27 The different types of peripheral pathophysiological pain are summarised in Table 7-3.

Peripheral neuropathic pain Peripheral neuropathic pain results from damage to the peripheral nervous system including the cranial nerves, spinal nerves and any of the peripheral nerves that branch from these. Typically the pain feels like it is coming from the parts of the body that the affected nerves innervate — that is, referred pain — and the pain often has a characteristic quality (e.g. burning or shooting). The term mononeuropathy is used where only

Mild pain

Moderate pain

Severe pain

Opioid + non-opioid

Non-opioid

± Adjuvant

± Adjuvant Paracetamol

NSAID

Codeine Tramadol

Oxycodone

Morphine Oxycodone

Hydromorphone Methadone

Fentanyl

Step 1

Step 2

Step 3

Advance up the ladder if pain persists

FIGURE 7-8

Strategy for pharmacological management of pain using the World Health Organization analgesic ladder. Multiagent therapy is usually required for optimal pain management. Patients with mild pain should be started on a non-opioid analgesic, and those with moderate pain on a step 2 opioid. Many patients can benefit from the addition of a non-opioid to the opioid (e.g. for bone pain) or an adjuvant agent to the opioid (e.g. for neuropathic pain). If this combination does not produce adequate relief or the patient presents with severe pain, step 3 opioids should be begun initially.

Perception Cortex

Thalamo- cortical

projections

Systemic opioids

Spinothalamic tract Primary afferent

nociceptor

Thalamus

Noxious stimulus

Local anaesthetics Transmission

Transduction

Epidural and local anaesthetics

FIGURE 7-9

Schematic diagram outlining the nociceptive pathway for transmission of painful stimuli. Interventions that prevent nociceptive transmission are shown at the points in the pathway that are thought to be their sites of action. Agents that block the transduction of pain actually prevent the generation of pain action potentials. In contrast, agents that block transmission actually stop the relay of action potentials to the cerebral cortex.

FIGURE 7-10

Surgical approaches to pain relief. Two approaches to the surgical alleviation of pain that target the axons of spinothalamic tract neurons as they project through the anterolateral funiculus, A, and cross the midline underneath the central canal, B.

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There is now compelling evidence to suggest that newborn children have the neural apparatus necessary to perceive pain. Despite this pain in young children is very poorly managed with analgesics administered infrequently or sometimes not at all. The evaluation of pain in infants and young children represents a significant challenge as they are unable to effectively communicate what they feel and may therefore receive inadequate pain control following traumatic injury or during painful medical procedures (Table 7-2). A number of behavioural assessment tools have been developed to

allow carers to obtain a quantitative estimate of pain in preverbal children. The most popular of these for both procedural and postoperative pain is the Face Legs Activity Cry Consolability (FLACC) scale. The presence of pain-related behaviours associated with each of these five components is scored from 0 to 2 giving an overall rating of 0 (no pain) through to 10 (severe pain). This scale has been used successfully in the assessment of pain in neonates through to teenagers where it is particularly useful in the assessment of individuals with impaired cognitive function.

PAEDIATRICS AND PAIN

TABLE 7-2 Pain perception in infants, children and the elderly

INFANTS CHILDREN THE ELDERLY

Pain threshold Painful neonatal experiences increase pain sensitivity Lower or the same as adults

No increase compared with middle age

Physiological symptoms

Increased heart rate, blood pressure and ventilatory rate; flushing or pallor, sweating and decreased oxygen saturation

Same as infants; nausea and vomiting

Same as infants and children; nausea and vomiting

Behavioural responses

Changes in facial expression, crying and body movements, with lowered brows drawn together; vertical bulge and furrows in the forehead between the brows; broadened nasal root; tightly closed eyes; angular, square-shaped mouth, chin quiver; withdrawal of affected limbs, rigidity, flailing

Individual responses vary

Individual responses vary and may be influenced by the presence of painful chronic diseases

TABLE 7-3 Clinical features and likely pathophysiology of peripheral neuropathies

PAIN SYNDROME PATHOPHYSIOLOGY CLINICAL FEATURES

Complex regional pain syndrome (type II)

Traumatic injury of peripheral nerves causing spontaneous action potentials to be generated in both damaged and intact nociceptors

Ongoing pain, allodynia, hyperalgesia, oedema, cutaneous blood flow and sweating abnormalities

Painful diabetic neuropathy Hyperglycaemia leading to degeneration of unmyelinated sensory neurons

Loss of sensation and burning pain in feet and hands

Postherpetic neuralgia Infection of peripheral nerves with varicella zoster virus leading to sensory neuron loss

Loss of sensation, pain and allodynia in dermatome of infected nerve

Lumbosacral radicular pain Herniated intervertebral disc, resulting in compression injury of spinal nerve causing spontaneous activity in nociceptors

Lancinating (stabbing, piercing sensation) pain in the thigh or lower leg

Phantom limb pain Spontaneous activation of nociceptors in neuroma and sensitisation of central neurons as a result of nerve transection during amputation

Ongoing cramping or aching pain referred to amputated limb

Trigeminal neuralgia (Tic douloureux)

Compression of the trigeminal nerve (sometimes by an atypical blood vessel) as it enters the brain

Episodes of severe, sharp, piercing pain referred to the facial region sometimes triggered by light touch

Chemotherapy-induced peripheral neuropathy

Chemotherapy-induced neurotoxicity of myelinated primary sensory neurons

Loss of sensation and spontaneous burning pain

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150 PART 2 ALTERATIONS TO REGULATION AND CONTROL

a single nerve is involved and polyneuropathy is used where multiple nerves are affected. The nerve damage that causes the pain can be the result of a range of factors, including physical injury, disease, infection or poisoning (e.g. chemotherapy).

One of the most common causes of painful peripheral neuropathies is where a peripheral nerve is damaged by a traumatic injury. The damage can be caused by a variety of mechanical insults such as nerve compression (following a crush injury) or transection (as the result of a penetrating injury or surgical procedure). The resultant pain is severe, often has a burning quality and is characterised by both hyperalgesia and allodynia. These types of pain used to be referred to as causalgias but are now known as complex regional pain syndromes (CRPSs).28

Painful diabetic neuropathy is an example of a neuropathic pain caused by either type 1 or type 2 diabetes mellitus. Unfortunately, it occurs in more than 50% of individuals with long-standing diabetes. Painful diabetic neuropathy appears to be due to hyperglycaemia, as the pain can be reduced in severity and delayed in onset by careful control of blood glucose levels.29 The longer the length of the axons, the more susceptible the neurons are to hyperglycaemia, which is why painful diabetic neuropathy is usually characterised by numbness and burning pain in the distal extremities (a ‘stocking and glove’ type distribution) (see Figure 7-11) that gradually spreads proximally and becomes more severe.30 The lack of sensation in the affected areas may result in the formation of ulcers, which may require limb amputation if they become gangrenous. The major cause of the painful neuropathy appears to be degeneration of unmyelinated axons caused directly by hyperglycaemia, as well as ischaemia caused

by hyperglycaemia-induced damage to the blood vessels supplying the peripheral nerves. Further descriptions of diabetes are in Chapter 35.

Infections of the peripheral nerves can also result in neuropathic pain. About 20% of Australians will experience shingles (herpes zoster) during their lifetime. In shingles, the virus responsible for chickenpox (varicella) can lie dormant in the sensory nerves for years and then spontaneously erupt to cause a rash and painful blisters in the skin innervated by the infected nerves. Although the rash and blisters usually heal, in some sufferers the pain persists and is referred to as postherpetic neuralgia.

Given the diversity of causes of these peripheral neuropathies, it is perhaps not surprising that the mechanisms that underlie them differ and indeed in many cases remain poorly understood. Probably one of the better understood pathologies is that following a traumatic injury of a peripheral nerve responsible for CRPS. Where the nerve is completely transected (cut) or crushed, the portions of the axons distal to the injury typically degenerate because they are separated from their supporting cell bodies in the posterior root ganglia. This results in sensory loss due to the denervation of the peripheral tissue innervated by the affected nerve, as well as the formation of a neuroma at the site of the nerve damage. A neuroma consists of a disorganised array of scar tissue, neuroglial cells and inflammatory cells, as well as the axons of neurons attempting to regenerate along the damaged nerve and reinnervate the peripheral tissues. The regenerating axons within the neuroma itself appear to be highly sensitive and this is partly responsible for some of the symptoms associated with this type of injury. Action potentials appear to arise spontaneously from the neuroma, which may partly explain the pain in the absence of any peripheral stimuli. The structure itself is also very sensitive to mechanical stimuli, with gentle tapping of the skin overlying the neuroma or movement of the affected limb enough to elicit action potentials and produce pain.31

In some patients, the sympathetic nervous system also appears to play a role in CRPSs, because local anaesthetic blockade of sympathetic ganglia (or pharmacological block of adrenergic receptors) alleviates the pain. This pain appears to be a consequence of intact nociceptors in tissues that have been denervated by the nerve injury, that then become sensitive to noradrenaline released from sympathetic postganglionic neurons nearby.32 These intact nociceptors (which have axons in nerves not affected by the peripheral nerve injury) become sensitised and exhibit spontaneous activity and augmented responses to peripheral stimuli.

In addition to these changes in the properties of primary sensory neurons brought about by damage to the nerve, there is evidence to suggest that changes in the properties of neurons within the central nervous system may also contribute to neuropathic pain. Second-order neurons in the parts of the spinal cord receiving input from damaged

FIGURE 7-11

Painful diabetic neuropathy. In poorly controlled diabetes, hyperglycaemia affects the longest sensory neurons first. A Normal intact nervous system. B Diabetes-affected nervous system with degeneration of axons in the distal extremities, resulting in C diabetic neuropathy with the characteristic ‘stocking and glove’ distribution.

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nerves exhibit higher rates of spontaneous activity, show greatly enhanced responses to nociceptive stimuli applied to the periphery and become sensitive to low-intensity stimuli. The enhanced responsiveness of these neurons in the central nervous system is referred to as central sensitisation and appears to be a consequence of changes in the excitability of the second-order neurons themselves, as well as a reduction in the ongoing inhibitory influence exerted on these neurons by endogenous pain control circuits (disinhibition). Together with the peripheral mechanisms detailed above, these central changes are thought to be responsible for the spontaneous pain, hyperalgesia and allodynia associated with some forms of neuropathic pain.

Central pain syndromes Forms of pain caused by damage to the central nervous system are known as central pain syndromes. Such forms of pain are typically very intense, aching, shooting pains that feel like they are due to damage to peripheral tissues but where clinical examination fails to identify any peripheral tissue damage or peripheral nervous system pathology. The causes of central pain syndromes were first identified by postmortem examination of the brains of individuals with CRPSs, which revealed damage in parts of the brain and/or spinal cord known to be involved in the processing of pain.33 The damage may be the result of a number of factors, including traumatic injury, tumour, stroke or even the side effects of neurosurgery (see Table 7-4). Because the cause of the pain is not visible, such pain can be partic ularly frustrating for patients and diagnosis can sometimes be a long and challenging process.

TABLE 7-4 Causes of central pain syndromes

Vascular lesions (infarction, haemorrhage) Traumatic brain injury Neurosurgery Brain tumours Multiple sclerosis Spinal cord injury Epilepsy

FOCUS ON LEARNING

1 Explain the difference between mononeuropathy and polyneuropathy.

2 List some of the factors that can result in peripheral neuropathic pain.

3 List some of the causes of central pain. 4 Discuss the neural mechanism thought to be responsible

for painful diabetic neuropathy.

AGEING AND PAIN

The elderly typically experience a higher incidence of pain compared to other adults and as the population ages it is estimated that chronic pain is likely to affect about 5 million Australians by 2050. The impact of pain in older people can have particularly devastating consequences on their quality of life when it impacts upon their mobility and ability to socialise. The assessment of pain in the elderly can be challeng- ing as some perceive it as an inevitable consequence of ageing or fear the financial burden they perceive may be associated with it. The fact that the pain may also present with co-morbidities, including cognitive decline, makes the diagnosis and effective management of pain in older Australians a complex and time-consuming task (Table 7-2).

Given the difficulties associated with assessment of pain in the elderly it is perhaps not surprising that the treatment of pain in older adults is also problematic. Some patients simply don’t believe that their pain can be alleviated, while others are reluctant to take opioid analgesics because of their euphoric side effects or fear of addiction. This is unfortunate as employment of opioid analgesics may be more appropriate given the adverse effects of NSAIDs particularly in individuals with impaired liver or kidney function. Interestingly complementary and alternative medicine approaches seem to be widely accepted by the elderly as alternatives to drugs.

The mechanisms responsible for central pain syndromes are not well understood, but it is likely that damage to spinothalamic tract neurons and thalamocortical neurons by the original insult is responsible for triggering ongoing activity in neurons at subsequent levels of the pain pathway. It has been postulated that this activity may be a response to the loss of normal input to these neurons (caused by the damage earlier in the pathway) or the loss of normal inhibitory influences that normally suppress their activity.

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152 PART 1 ALTERATIONS TO BODY MAINTENANCE152 PART 1 ALTERATIONS TO BODY MAINTENANCEchapter SUMMARY

The definition of pain • Pain is clinically important as it encourages patients to

seek medical help and adopt behaviours that enhance healing.

• Pain has an important physiological role as it teaches us to avoid environmental stimuli that cause harm.

• Individuals born with a congenital insensitivity to pain suffer horrendous injuries because they are unaware of the damage they are experiencing.

• Pain is a subjective sensation that is affected by a large number of variables and consequently can be difficult to define.

• The International Association for the Society of Pain’s definition of pain highlights most of the key elements of pain.

• Pain is invariably unpleasant (it is a negative experience) and is therefore something we avoid.

• The ability to locate a painful stimulus and determine its intensity and quality is referred to as the sensory- discriminative aspect of pain.

• Pain produces changes in both mental state (affect) and behaviour (motivation), which are referred to as the affective-motivational aspect of pain.

• Pain is usually the result of tissue damage but can be caused by stimuli that would cause tissue damage if sustained.

• The threshold for pain is lower than the threshold for tissue damage.

• The intensity of the pain experience can be modified by behaviour, cognitive factors and clinical intervention.

Types of pain • Nociceptive pain due to external damage is relatively

mild and has a comparatively short time frame. • Nociceptive pain due to internal damage is less common,

is usually more severe and has a longer time frame. • Neuropathic pain is caused by injury or disease of the

nervous system and can be both severe and persistent. • Psychogenic pain is the result of a psychological disorder,

but for the patient it can be just as severe and debilitating as nociceptive pain or neuropathic pain.

Pain terminology • Pain is described as either acute or chronic and these

classifications are independent of aetiology. • Chronic pain affects about 20% of Australians. • Referred pain is perceived as originating from a part of

the body distinct from the site of tissue damage. • Hyperalgesia is where there is increased pain in response

to a stimulus that is normally painful. • Allodynia is where pain results from a stimulus that does

not normally produce pain. • The conscious perception of tissue damage occurs in the

cerebral cortex.

The physiology of pain • A three-neuronal pathway relays information about

peripheral tissue damage from the periphery to the cerebral cortex Nociceptors are the first-order neurons in the pain pathway.

• There are two classes of cutaneous nociceptor: high- threshold mechanoreceptors and polymodal nociceptors.

• Joints, muscle and viscera appear to be innervated by neurons with properties similar to cutaneous polymodal nociceptors.

• Joints, muscle and viscera also appear to be innervated by silent (or ‘sleeping’) nociceptors that only become active when these tissues become inflamed as the result of damage or disease.

• Although there are a number of neural pathways relaying information about tissue damage between the spinal cord and brain, the most important in terms of the conscious perception of pain is the spinothalamic tract.

• Spinothalamic tract neurons are the second-order neurons in the pain pathway and they collect the information delivered to the spinal cord by nociceptors and relay this to the thalamus.

• The axons of spinothalamic tract neurons are sometimes targeted in surgical approaches to the treatment of severe chronic pain through a midline myelotomy or anterolateral cordotomy.

• Spinothalamic tract neurons terminate in two structurally distinct regions of the thalamus.

• Thalamocortical neurons with their cell bodies in the posterolateral parts of the thalamus relay information about tissue damage to the somatosensory cortex and interoreceptive cortex.

• Thalamocortical neurons located in the medial thalamus relay information about peripheral tissue damage to the anterior cingulate cortex.

• Through the information that they receive from the posterolateral parts of the thalamus, the somatosensory and interoreceptive cortices are thought to be responsible for the sensory-discriminative aspect of pain.

• The medial thalamic projection to the anterior cingulate cortex is thought to be responsible for the affective- motivational aspect of pain.

• Neuropathic pain affects up to 7% of the population and contributes significantly to the cost of healthcare in developed countries.

• Modulators of pain include substances that stimulate pain receptors (i.e. prostaglandins, bradykinins, substance P, glutamate) and substances that suppress pain (i.e. endorphins, gamma-aminobutyric acid (GABA), serotonin).

• Endorphins are endogenous opioids that attach to opioid receptors and inhibit transmission of pain impulses. Encephalins are other opioid peptides.

• They are present in varying concentrations in the neurons of the brain, spinal cord, and gastrointestinal tract.

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A D U L T Peter was a 59-year-old shearer whose best friend was a blue heeler called Red. After noticing blood in his stools Peter visited his local general practitioner and was subsequently diagnosed with carcinoma of the colon. A colon resection was performed and he underwent a complete course of radiotherapy and chemotherapy. Six months later, Peter started to experience abdominal pain. On investigation it was revealed that the malignancy had spread into his urinary bladder and urethra. Peter was readmitted to hospital and in subsequent weeks his pain increased progressively until eventually it could only be controlled with high doses of intravenous morphine.

Twelve months after the onset of the pain, Peter had a midline myelotomy in the mid-thoracic region of the spinal cord. Ten days following this operation, he was able to leave hospital and lived pain-free until his death 5 years later. 1 Explain the physiology of Peter’s abdominal pain. 2 Discuss how morphine controls acute pain. 3 Explain why Peter was likely to experience ongoing pain

that was responsive only to high-dose morphine. 4 Outline the aim of a midline myelotomy. 5 Explain why you think a midline myelotomy might

provide a better outcome for pain of visceral origin.

Clinical manifestations of pain • Pain tolerance is the duration of time or the intensity of

pain that an individual will endure before initiating overt pain response.

• Pain threshold is the point at which pain is perceived. • Pain is a subjective symptom but can result in activation

of the autonomic nervous system activation, which causes an increase in heart rate, blood pressure and ventilation, nausea and vomiting as well as sweating.

Evaluation and treatment • Evaluation of pain is often difficult; the patients’

experiences and objective measures guide therapies. • Treating the original cause of pain should be

addressed first, followed by pharmacological and non- pharmacological therapies.

Paediatrics and ageing and pain • Newborns and young children have the anatomical and

functional ability to perceive pain. Older individuals tend to have a slightly higher pain threshold, probably because of changes in the thickness of the skin and peripheral neuropathies.

Pathophysiology of pain • Peripheral neuropathic pain results from damage to the

peripheral nervous system.

• Peripheral neuropathic pain can be the result of physical injury, disease, infection or toxicity.

• Mononeuropathy is where only a single nerve is involved and polyneuropathy is where multiple nerves are affected.

• The neural mechanisms responsible for painful peripheral neuropathies are complex and in many cases remain poorly understood.

• Following a traumatic injury of a peripheral nerve the portions of the axons distal to the injury sometimes degenerate and a neuroma may form at the site of the nerve damage.

• Action potentials can occur spontaneously in the neuroma and it may be very sensitive to mechanical stimuli, resulting in pain if it is touched or disturbed by movement.

• In some cases noradrenaline released from sympathetic postganglionic neurons appears to exacerbate the pain produced by nerve injury.

• Central sensitisation of spinothalamic tract neurons is also thought to contribute to peripheral neuropathic pain.

• Central pain syndromes are characterised by very severe persistent pain caused by traumatic injury, tumour, cerebrovascular incidents or brain surgery.

CASE STUDY

A G E I N G Cecil, an 86-year-old man, who worked as a tradesman until his retirement 16 years ago presents to the doctor with lower back pain. He is generally active, playing lawn bowls twice a week, and walking three times per week for 30 minutes each time but his lower back pain is starting to restrict these activities.

Upon questioning, Cecil related that the lower pain had affected him for the last 10 years of his working life and had gradually become more severe during retirement. When he was physically examined, there was acute tenderness over L2–L4, but Cecil only rated the pain as 3 out of 10. There were no obvious signs detected. The doctor was unsure of the origin of the lower back pain and Cecil was instructed to have

imaging studies using magnetic resonance imaging (MRI) and prescribed a non-steroidal anti-inflammatory medication to be taken when he experiences pain. 1 Explain the likely physiology of Cecil’s lower back pain. 2 Based on the lack of signs and symptoms experienced

by Cecil, is the MRI scan likely to identify an anatomical reason for the lower back pain?

3 What is the significance of acute tenderness over L2–L4? 4 Discuss the effectiveness of NSAIDS for pain management

in older people. 5 Provide reasons why Cecil may perceive his pain at a

lower level than expected.

CASE STUDY

CHAPTER 7 PAIN 153

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154 PART 2 ALTERATIONS TO REGULATION AND CONTROL

1 Outline the features of the pain experience that are included in the sensory-discriminative aspect of pain.

2 Explain why it is useful for the threshold for pain sensation to be lower than the threshold for tissue damage.

3 Discuss the difference between hyperalgesia and allodynia.

4 Compare and contrast the properties of cutaneous high- threshold mechanoreceptors and polymodal nociceptors.

5 Explain why a skin laceration often causes two pain sensations separated in time.

6 Discuss why a painful stimulus applied to the right side of the body results in activation of the cerebral cortex on the left side of the body.

7 Explain the difference between a midline myelotomy and an anterolateral cordotomy.

8 Which cortical sites are thought to be involved in the conscious perception of pain? In which lobes of the cerebral cortex are they located, and what is their postulated function?

9 Outline some of the pathophysiological mechanisms thought to underlie the neuropathic pain that may arise from a peripheral nerve transection.

10 What is responsible for the nerve damage arising from painful diabetic neuropathy?

R E V I E W Q U E S T I O N S

ch07-137-154-9780729541602.indd 154 18/09/14 9:26 AM

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Understanding pathophysiology CH 7 - Pain