Nociception or neuropathy

Pain is universally viewed as a primary indicator of underlying tissue pathology and pain is also one of the main reasons that people visit health professionals (Coda & Bonica 2001). When considering the biological contributors to the experience of pain, we can divide pain into two types, depending on the structures and mechanisms involved. Nociceptive pain refers to pain arising from injury or pathology in the tissues, for example, soft tissue sprains and strains, bone fractures or appendicitis. Neuropathic pain, on the other hand, refers to pain arising from pathology to or changes within the peripheral and central nervous system. Nociceptive pain is generally described as aching or dull and, in the case of musculoskeletal pain, usually related to activity or posture. By contrast, neuropathic pain is frequently described as burning or shock-like and is associated with a region of sensory disturbance (Siddall in press). Episodes of neuropathic pain can occur spontaneously or as an exaggerated response to minor stimulation. An exaggerated response to a non-painful stimulus, such as light touch, is called allodynia. An exaggerated response to a painful stimulus is called hyperalgesia. Pain can further be classified clinically as acute or chronic. These distinctions are important as different types of pain, with different characteristics and underlying mechanisms, have different responses to treatment.

Table 12.1 Differentiating nociceptive pain from neuropathic pain

PAIN PROCESSING IN THE PERIPHERAL AND CENTRAL NERVOUS SYSTEM

Understanding the nature of pain has consumed humankind throughout the ages. During the 19th and 20th centuries, advances in the study of anatomy, physiology and histology prompted the formulation of several physiologic theories of pain. Of these, the gate control theory (Melzack & Wall 1965) was the most influential and the first attempt to combine neurophysiological mechanisms with psychological processes such as cognitions and emotions. In this model, pain was viewed as an end product of a number of interacting processes in which the central nervous system played an active role in determining the nature and degree of pain following harmful stimulation in the periphery. Although we now know that this theory is overly simplistic, it nevertheless provides us with an understanding of the types of mechanisms involved in the processing and modulation of the experience of pain.

A simple explanation of the nervous system changes that occur in response to pain is that injury, disease or inflammation in tissues activates local nociceptor terminals to transmit information about physical damage to the dorsal horn of the spinal cord. These nociceptors become sensitised by the release of chemicals from the damaged tissue and by the release of neurotransmitters from sensory nerve endings. This process is called peripheral sensitisation and is responsible for primary hyperalgesia or increased sensitivity to mechanical and thermal stimulation at the site of injury or pain. Once noxious information reaches the spinal cord, it is modulated by cells within the spinal cord and by the activation of descending pathways from the brain, which might be either inhibitory or excitatory. Continued transmission of noxious information from the periphery leads to a cascade of events within the central nervous system (spinal cord and brain) that contribute to an increase in responsiveness of central neurons. This is known as central sensitisation.

In the case of neuropathic pain following peripheral nerve injury, the peripheral processes of nociceptors can become traumatised and undergo numerous changes that lead to increased activation of peripheral and central pain circuits that sometimes become chronic and debilitating. Allodynia, hyperalgesia, dysaesthesias (unpleasant abnormal sensations) and spontaneous pain are common features of neuropathic pain and are mediated by central sensitisation.

Under normal conditions central sensitisation resolves following recovery. In some cases, however, central changes persist and symptoms associated with these changes are seen in pathological pain states such as complex regional pain syndrome (CRPS), failed back surgery syndrome and phantom limb pain.

From the spinal cord, noxious signals reach the brain via a number of ascending tracts that terminate in many structures throughout the brainstem, thalamus and cortex (Fields 2004). The thalamus acts as a major relay station in the transmission of noxious signals. As these signals reach the brain, many other regions are also activated, including those that control a number of autonomic and homeostatic mechanisms such as blood pressure regulation and respiration (Siddall & Cousins 2004). In addition, there are descending mechanisms mediated by a variety of neurotransmitters, acting at subcortical and spinal cord levels, modulating ascending information (Fields 2004).

The higher brain centres used in pain processing can be divided into those involved in the sensory-discriminative component of pain perception (somatosensory cortex) and the affective component of pain perception (such as cingulate cortex). However, this may be an oversimplification. Functional imaging studies have now identified a widely distributed network of cortical and subcortical areas that are activated by noxious stimuli (Ingvar 1999). These include sensory, limbic, associative and motor areas. Functional imaging studies have also shown significant differences in brain activation between people with no pain, acute pain and chronic pain (Apkarian et al 2005). Figure 12.2 shows the mechanisms of pain.

Figure 12.2 Pain mechanisms

Pain perception

Pain does not occur in isolation but, rather, within a context that has a direct bearing on the person’s perception of pain and on their response to pain (Siddall in press). Pain can be extremely variable; it can attain intolerable intensity, persist beyond tissue healing or disappear in the heat of battle. The way we interact with our environment is significantly affected by pain. Our behaviour also changes over time as the pain state continues.

Given the IASP definition of pain as an experience that is modulated by a complex set of emotional, environmental and psychophysiological variables, one would expect that pain would influence brain processing on many levels (Ingvar 1999). The neural representations of the mechanisms involved in pain modulation – for instance, the influence of learning, meaning, attention, anticipation or avoidance – should also be taken into account when one considers the representation of pain at the neural level.

A number of research techniques have been used to study these neural representations:

In recent years, functional imaging has added significantly to our knowledge of where and how pain is processed in the brain (Bushnell 2005). As pointed out earlier, the processing of pain can no longer be viewed as a simple ‘hard-wired’ system with a strong relationship between stimulus and response (Siddall & Cousins 1997). We now have a better understanding of the neuroplastic changes that occur within the central nervous system in the presence of pain and hence the changes that should be addressed as part of an integrative approach to pain management (Siddall in press).

Attitudes and beliefs

What the pain means to a particular person at a particular time will have a clear influence on how that person subsequently responds. For example, if a person wakes in the night with stomach pain, he or she may think ‘I should not have eaten so much’, groan, roll over and eventually fall back to sleep. However, if they think that the pain may be an indicator of stomach cancer, perhaps because they saw a program on television about stomach cancer the previous evening or because they have a close relative with that disease, they are then likely to begin monitoring the pain, become worried and distressed, be unable to fall back to sleep and so on. Chapman and Okifuji (2004) discuss three main cognitive factors that will influence the pain experience:

Chapman and Okifuji (2004) point out that studies have shown all three factors to have an impact at the physiological level. For example, skin conductance in headache patients is elevated in response to seeing words relating to migraines on a screen (Jamner & Tursky 1987).

Psychological distress (suffering)

For many people pain, by definition, entails suffering. Nevertheless the degree of suffering is clearly variable and likely to be influenced by a range of factors. For example, the duration, severity, frequency and number of sites of pain (Fishbain et al 1997) may impact on the level of suffering. Williams (1998) points out that a person in pain may experience a wide range of losses both material and intangible, covering everything from employment and finances, to changes in relationships, being able to maintain independence, issues of self-worth and so on. They also often experience symptoms such as fatigue, difficulty concentrating, muscle tension, disturbed sleep, side effects of medication and deconditioning. In addition they may have to deal with a range of health professionals, with possible disbelief and lack of understanding from some and undergo a variety of tests and interventions. They may have numerous fears or worries, including fear about the cause of the pain or that the doctors have missed something, fear of re-injury, worries about the future, financial concerns and so on.

The important point to note here, in terms of a biopsychosocial model, is the way in which each of these factors has the potential to impact on every other factor. For example, a person may avoid certain activities as a result of pain, experience weight gain, deconditioning and loss of social contact as a result, followed by a drop in mood. Then, due to low mood, they have great difficulty in being motivated to become active again and thus the low mood and deconditioning become further entrenched.

There is often considerable overlap between the symptoms of mood disturbance and those caused by the pain or factors related to it such as inactivity and the side effects of medications. For example, disrupted sleep, low energy, poor concentration, sexual dysfunction and weight changes can be the result of any of these.

Given all the issues faced by people with persistent pain it is not surprising that a large proportion may be diagnosed as having depression or an anxiety disorder. Although issues of measurement and definition make establishing prevalences difficult (Williams 1998), few would dispute that it is a major issue for a large number of such people. Studies in the area of depression suggest a wide range of prevalences ranging from 10 to as high as 100% but with the majority reporting it in over 50% of cases (Sullivan 2001).

There has been much debate about the relationship between depression and chronic pain, particularly regarding the question of whether pain causes depression or depression leads to pain (Fishbain et al 1997). A comprehensive review of the literature on the pain–depression association by Fishbain found little evidence for the hypothesis that depression leads to pain while all studies relating to the hypothesis that pain can lead to depression had results consistent with that hypothesis. In addition, increased pain led to increased depression rather than the other way around. Having said that, it would of course always be important to establish if there is any history of depression or other psychiatric illness.

Post-traumatic stress disorder (PTSD) and chronic pain can share a specific relationship in that very often the accident or trauma that occasioned the ongoing pain has also caused post-traumatic stress symptoms (see Sharp & Harvey 2001). For example, as a result of a motor vehicle accident, a person may experience pain from physical injuries and post-traumatic stress symptoms relating to the accident. Not surprisingly, as with depression, having PTSD and chronic pain means an additional load and likely interactions for the patient. This means both must be addressed.

FEAR AVOIDANCE

People in pain can evidence a high level of ‘fear avoidance’, such that they become fearful of engaging in physical activity due to the risk of increased pain and/or (re)injury and therefore avoid the activity (see Fig 12.3) (Vlaeyen et al 1995, Vlaeyen & Linton 2000). Over time this can result in significantly reduced activity levels, increased disability, deconditioning and depression or distress. Fear avoidance provides an excellent example of the interaction of three separate levels of the biopsychosocial model. Beliefs or appraisals of pain at one level result in anxiety or fear at the next level that, in turn, results in disability or pain behaviours at the next. The latter then further entrench the negative aspects of the pain experience and thus fear avoidance becomes established. Leeuw et al (2007) recently published a comprehensive review of the current evidence for the fear-avoidance model.

Figure 12.3 The fear-avoidance model

Pain behaviour

As pointed out by Fordyce (1976), the only way in which we can know that a person is in pain is by their display of pain behaviour; by observing what they do or do not do and what they tell us. There is no objective measure of pain available to us other than this. Moreover, as pointed out earlier in the chapter, there is often no correlation between what we observe in this regard and identifiable tissue damage. Pain behaviours can take many forms from grunting, moaning and groaning, to limping, distorted posture and being hunched over. People may tell you that they are in pain but equally their lack of social engagement may be an indicator of discomfort. They may take medication, attend numerous medical appointments or treatments and they may take time off work, lie down or cease activities. Equally they may rate their pain as being very high on questionnaires or in response to questions about their pain. It is important to note in relation to pain behaviours that, because pain is a completely subjective experience and because there are no objective measures, health professionals can only go by the person’s report. A change in such behaviours and reports can at least indicate that, for that person, at that time, there has been a change in their experience of the pain. Note also, suggesting to a person that they are not in pain may only serve to increase the display of pain behaviour. The important point here is that if pain is viewed as an experience, the distinction between real, exaggerated or fabricated pain becomes irrelevant. For health professionals the targets of treatment become not the pain itself but the associated suffering or disability (Fordyce 1988).