Pain



Pain


Lester Jones, G. Lorimer Moseley and Catherine Carus (Case study development)



Introduction


Pain is a common and normal human experience. Pain helps us to learn to adopt protective behaviour when we are threatened and safe behaviour when our body has been injured. Pain usually seems like a reasonably predictable experience. In a normal state, receptors in the tissues of the body respond at reasonably predictable thresholds of stimulation. When they do respond, they initiate action potentials that travel along peripheral neurones into the spinal cord. Neurotransmitters released from these neurones often activate secondary neurones, which send action potentials up the spinal cord to the brain. The brain then evaluates this information. Often, pain is perceived in the tissues that were stimulated. This might seem simple, but it is not.



There are several key parts of this definition.



• Firstly, although the nociceptive system is critical for detecting dangerous stimuli and alerting the brain, pain is not simply the transmission of noxious sensory information (nociception). Rather, pain has potentially profound cognitive and emotional influences, just like other perceptual states (even vision – think of your favourite visual illusion and notice that what you see is not necessarily an accurate reflection of the light that is hitting the light receptors on your retina).


• Secondly, pain is not a measure of tissue damage, which means that tissue can be injured but not painful, and painful but not injured.


• Thirdly, pain is about threat to body tissue, not about a particular mode of sensory input. This sets pain apart from other information that is sent from our tissues to our brain: the so-called somatic senses. It is this threat-specific quality that makes pain critical for protection and preservation of the body: pain seems to be the conscious component of a complex defence system.


• Finally, there are many unconscious components of this defence system, all of which can influence each other and influence pain. Thus, pain is a fundamentally conscious process, which is preceded and accompanied by a range of responses, most of which are not conscious. According to this model of pain, when someone is in pain, we can be sure that their brain is concluding that tissue is in danger and that they should take some sort of action to get the tissues out of danger (Wall 1999; Butler and Moseley 2003).



The physiology of pain


This section will discuss the physiology of pain under three categories:



Within each category, we will separate peripheral from spinal and brain mechanisms, when it is appropriate to do so.



Activation of the nociceptive system


Peripheral transmission


The peripheral nervous system is well studied but not completely understood. Many types of neurones in the periphery are thought to contribute to nociception (Meyer et al. 2006). The most important of these neurones are probably Aδ and C fibres – conventionally called nociceptors – although many Aδ and C fibres also respond to non-noxious inputs (Craig 2002).


For the sake of clarity, we will classify Aδ and C fibres as primary nociceptors (see Table 17.1).



Nociceptors are found in most tissues of the body and can be considered to have the principal role of detecting dangerous thermal, mechanical or chemical stimuli. Studies have attempted to identify activation thresholds for different noxious stimuli (the activation threshold is the lowest intensity of a stimulus that produces an action potential in the nociceptor). While there is variability between individuals, there seems to be a predictable range of activation thresholds for primary nociceptors in healthy pain-free individuals.




Spinal transmission


Primary nociceptors terminate in the dorsal horn of the spinal cord. The dorsal horn consists of numerous layers, which are defined according to the projections and structural and functional properties of their neurones. The majority of nociceptors terminate in laminae I (Aδ fibres usually terminate here), II (C fibres usually terminate here) and V (Aδ, C and Aβ fibres all terminate here). Lamina II neurones project to other laminae and can be excitatory or inhibitory. Because peripheral input onto lamina I fibres is almost exclusively nociceptive (Aδ), the neurones that project from here are called nociceptive-specific second order neurones. Because peripheral input onto lamina V second-order neurones includes Aδ, C and Aβ fibres, lamina V second-order neurones tend to respond over a wide range of stimulus inputs, which is why they are called wide-dynamic range neurones.




Brain transmission


The brain is defined here as that part of the CNS that lies above the spinal cord. There are several important characteristics of how nociception is handled by the brain.



Parallel processing

Many brain areas are involved in pain. Most often, the thalamus, insula, primary (S1) and secondary (S2) somatosensory and prefrontal cortices are involved. These areas are called the pain matrix (Apkarian et al. 2005) (Figure 17.1). However, these areas are never the only areas involved and they are not always all involved – the pattern of brain activation varies greatly between, and within, individuals.




Different aspects of pain seem to involve different brain areas

In an attempt to clarify the potential roles of different brain areas in pain, some authors conceptualise two systems. The medial nociceptive system includes the medial thalamic nuclei, anterior cingulate and dorsolateral prefrontal cortices. It is described as slow and only broadly somatotopic, which means it does not have the capacity to code in detail the location in the body at which the stimulus occurred. Activity in this system has been proposed to subserve the affective-emotional dimensions of pain, i.e. the unpleasantness of pain rather than the intensity and quality. This aspect of pain may have value to the person experiencing pain by triggering behaviour that demands other people’s attention (Goubert et al. 2009).


The lateral nociceptive system includes the lateral thalamic nuclei and the primary (S1) and secondary (S2) somatosensory cortices. It is described as fast and is highly somatotopic, which means it is able to code, in great detail, the tissue location at which the stimulus occurred. Activity in this system is proposed to subserve the sensory-discriminative aspects of pain, i.e. the intensity of the pain and the sensory characteristics of the stimulus (e.g. warm, sharp, deep, superficial). The intensity and unpleasantness of pain can be independently manipulated (e.g. Moseley 2007a).



Multiple inputs: The neuromatrix theory

Melzack (1990) proposed the neuromatrix theory as a way of conceptualising how myriad inputs and factors affect pain and nociception (Figure 17.2). Inputs and factors in that theory include previous learning and past experiences, immune and endocrine states and responses, activity in the autonomic nervous system, and information coming from nociceptors and other sensory receptors. The theory suggests that pain will occur when all these elements are evaluated and a specific network of neurones in the brain is activated. Melzack calls each particular network of neurones a neurosignature (or ‘neurotag’ (described by Butler and Moseley (2003)), which is analogous to the representation concept used in cognitive neuroscience literature (see Damasio (2000) for a review of representation theory). Remember that this is a theory and that the brain physiology underpinning pain and consciousness is not well understood.





Sensitisation of the nociception/pain system


The nociceptive system is dynamic. If the system becomes more sensitive than usual, it often results in hyperalgesia (things that hurt now, hurt more) and allodynia (things that didn’t hurt now do).



Hyperalgesia and allodynia might be expected and seem intuitively sensible after recent damage to tissue, but they are also a predominant feature of persistent pain. It is unlikely that the same processes are involved in hyperalgesia and allodynia in acute post-injury pain, and hyperalgesia and allodynia in chronic pain.



Peripheral mechanisms


Peripheral mechanisms that increase the pain evoked by a standardised stimulus include the presence of inflammatory mediators (including proinflammatory cytokines, bradykinin, prostaglandins), decreased circulation (which increases the local concentration of H+ ions), the presence of immune mediators and activation of certain genes (Figure 17.2) (see Meyer et al. (2006) for an exhaustive review of peripheral mechanisms of modulation). Inflammatory mediators are released by tissue damage and by activation of nociceptors (neurogenic inflammation). This sensitisation, driven by peripheral mechanisms, is called peripheral sensitisation and the hyperalgesia that follows is called primary hyperalgesia.



Spinal cord mechanisms


Second order nociceptors can also become sensitised. The N-methyl-D-aspartate (NMDA) receptors in the dorsal horn respond to persistent or intense stimulation by opening channels to allow greater post-synaptic activity. This means that the same input from the periphery will result in greater activation of the second order nociceptor, which means that more messages of danger to body tissue will be sent to the brain.



Dorsal horn mechanism

NMDA receptors are important in central sensitisation. They are normally blocked by magnesium, but prolonged nociceptive activity and release of peptides can remove the block and allow glutamate to bind to the receptor. The resultant activation of voltage-sensitive channels allows an influx of calcium into the second order neurone. This process can lead to a change in the NMDA receptor so that the magnesium block then becomes less effective, which means that, next time, the sensitisation will happen more quickly.


There are other mechanisms in the dorsal horn that can sensitise the nociceptive system. Wide-dynamic-range neurones in the laminae of the dorsal horn provide an interaction of the processing for nociception and other sensory information. This may be important in how people describe their pain, sometimes referred to as the ‘quality’ of pain. It also provides a potential mechanism for further sensitivity of the nociceptive system, whereby the responses to normally non-painful stimuli, such as touch, are now painful. This may be because the wide-dynamic-range neurones synapse with sensitised neurones. Another mechanism of sensitisation involves the sprouting of neurones across laminae. Such sprouting may link a non-nociceptive peripheral nerve fibre (e.g. Aβ fibre) with an interneurone that would normally respond to noxious stimulation. This is probably more likely to occur after peripheral nerve injury or death. Butler and Moseley’s (2003) Explain Pain discusses these mechanisms in an accessible, but reasonably detailed, way.




Neuropathic pain


The pain associated with nerve damage is known as neuropathic pain and may include descriptions such as ‘burning’ or ‘electric shock’. CNS damage, such as stroke, can result in centrally-mediated neuropathic pain that reduces the inhibition of the nociceptive system. Peripherally, damage to an axon or the myelin covering of a nerve, can lead to spontaneous transmission of impulses from the damaged area or the dorsal root ganglion (DRG). This may also be driven, in part, by loss of inhibition, specifically through alterations of chloride homeostasis affecting gamma amino-butyric acid (GABA)-mediated inhibition (see review of mechanisms in De Koninck (2009) and also Sandkühler (2009)). Such damage will usually result in hypersensitivity to mechanical input. This sensitivity forms the basis for tests such as Tinel’s sign – sometimes considered as an indicator of neuropathic pain.


There is mounting evidence that interactions between the immune system, the endocrine system and the autonomic nervous system are important in all types of pain, including neuropathic pain (Watkins and Maier 2000).



Pain modulation via psychological and social influences


Anecdotal evidence that somatic, psychological and social factors modulate pain is substantial – sport- and war-related stories are common (see Butler and Moseley (2003) for several examples). However, numerous experimental findings corroborate the anecdotal evidence (see Fields et al. (2006) for a review of CNS mechanisms of modulation and Poleshuck and Green (2008) for a review of the impact of socioeconomic disadvantage and pain).


By far the greatest research efforts in this area have been directed towards the cognitive modulation of pain. Experiments that manipulate the psychological context of a noxious stimulus often demonstrate clear effects on pain, although the direction of these effects is not always consistent.



Despite the wealth of data, consensus is lacking: some data suggest that attending to pain amplifies it and attending away from pain nullifies it; others suggest the opposite. This may be explained by the existence of different modes of selective attention (see Legrain et al. (2009) for review). Most likely, the effect depends on the coping style of the individual and the wider context of the experiment or situation.



Anxiety


Anxiety also seems to have variable effects on pain. Some reports link increased anxiety to increased pain during clinical procedures (Schupp et al. 2005; Klages et al. 2006) and during experimentally-induced pain (Tang and Gibson 2005), but other reports suggest no effect (Arntz et al. 1990; Arntz et al. 1994). Relevant reviews conclude that the influence of anxiety on pain is probably largely dependent on attention (Arntz et al. 1994; Ploghaus et al. 2003).



Expectation


Expectation also seems to have variable effects on pain. As a general rule, expectation of a noxious stimulus increases pain if the cue signals a more intense or more damaging stimulus (Fields 2000; Sawamoto et al. 2000; Keltner et al. 2006; Moseley 2007a; Moseley and Arntz, 2007) and decreases pain if the cue signals a less intense or less damaging stimulus (Pollo et al. 2001; Benedetti et al. 2003). There are several informative reviews on the influence of expectation on pain (Fields 2000; Wager 2005).


The common denominator of the effect of attention, anxiety and expectation on pain seems to be the underlying evaluative context, or meaning, of the pain. That is demonstrated by the consistent effect that some cognitive states seem to have on pain. For example, catastrophic interpretations of pain are associated with higher pain ratings in both clinical and experimental studies (see Haythornwaite (2009)). Believing pain to be an accurate indicator of the state of the tissues is associated with higher pain ratings (Moseley et al. 2004), whereas believing that the nervous system amplifies noxious input in chronic pain states increases pain threshold during straight leg raise (Moseley 2004).



Social context


The social context of a noxious stimulus also affects the pain it evokes. For example, when men have blood taken by a woman, it hurts less than when it is taken by another man (Levine and De Simone 1991). The effects are variable but, again, seem to be underpinned by the underlying evaluative context or meaning (see Butler and Moseley (2003) for a review of pain-related data and Moerman (2002) for exhaustive coverage of the role of meaning in medicine and health-related interactions).


To review the very large amount of literature on somatic, psychological and social influences on pain is beyond the scope of this chapter. However, it is appropriate, and clinically meaningful, to reiterate the theme that emerges from that literature: the influences on pain perception, tolerance and report are variable and seem to depend on the evaluative context of the noxious input.



Assessment and measurement of pain


Pain is an essentially personal experience, which means measurement of pain relies on the person in pain communicating their experience. Therefore, any measure of pain, including report of pain, is really a measure of pain behaviour. Clinicians and researchers make a judgement according to how well they think the measure of pain behaviour might reflect pain, but, ultimately, this relies on assumptions that as yet cannot be verified. This limitation also applies to physiological measures, such as brain imaging.


Earlier in this chapter, we argued that pain depends on many modulating factors and can be expressed in many ways. Moreover, we argued that pain is one output of the brain that serves to protect the tissues. Those arguments mean that assessment and measurement of people in pain encompasses more than measurement of their pain. One framework that is useful in assessment of people in pain is the World Health Organization International Classification of Functioning, Disability and Health (WHO ICF).



The WHO international classification of functioning, disability and health (WHO ICF)


This section uses the WHO ICF as a framework for assessment and treatment planning of patients in pain. This framework is advocated by the IASP (Wittink and Carr 2008). The WHO ICF focusses on how a person is functioning and evaluates outcomes using the person’s actual performance in the real-life environment. This makes it especially useful for those patients where pain relief is not the only, and possibly not the most important, objective.


The WHO ICF has three components: the body (function and structure); activities and participation; and contextual factors (e.g. environmental factors that might influence function). Each component is classified at a level of severity (none, mild, moderate, severe, complete) and interactions between components are evaluated (WHO 2002). As it relates to people with pain, the three components of the ICF broadly mirror the components of the biopsychosocial model, which considers tissue-based, psychological and social influences on pain.



The interview


Most therapeutic processes will start with an interview. The interview aims to capture information about the person in terms of the ICF. Physiotherapy interviews have conventionally focussed on symptoms: location, intensity, quality and temporal patterns, and signs. This information is very important, but it is not sufficient. According to the ICF this information relates to the body, the biopsychosocial model’s equivalent of the tissues. However, we advocate, as do other reviews in this area (e.g. Gifford et al. 2006) that the interview must also provide information about activities and participation and contextual factors (i.e. the ‘psychosocial’), and how these issues may interact with pain and the state of the tissues (Goldingay 2006a, 2006b). The aim of the interview then is to identify factors from across biopsychosocial domains which activate or sensitise the nociceptive or pain system (see Table 17.2).




Measures and scales


Self-reporting measures


Assessing pain is a key aspect of the assessment process. Self-reporting measures are considered the gold standard in assessing pain intensity, location, quality and temporal variation.



Visual analogue scales (VAS) and numerical rating scales (NRS) are most common and useful. A visual analogue scale consists of a horizontal line, usually 100 mm long. At each end is a term of reference for the patient, called an anchor. The left anchor is usually ‘No pain’ and the right ‘worst pain’ or ‘worst pain imaginable’. The patient marks a point on the line in answer to a question about their pain and the distance from the mark to the left anchor is used as a measure of their pain. A NRS uses numbers instead of a line, such that 0 = ‘no pain’ and 10 = ‘worst pain’. The VAS is probably more sensitive to change, less vulnerable to perseveration (remembering what you said last time and responding the same way) and more difficult to measure. The NRS is easier to use clinically and is probably sufficiently sensitive to detect clinically meaningful changes [a clinically meaningful change is usually considered to be about two points on a ten-point scale (McQuay et al. (1997))].


Several tools assess the quality of pain. A simple tool is a VAS, with anchors reflecting the unpleasantness of pain. The most widely used is the short form of the McGill Pain Questionnaire (MPQ) (Melzack 1975a). The MPQ lists a variety of words that are grouped as being about the sensory-discriminative aspect of pain (e.g. sharp, burning, intense), the affective aspect of pain (e.g. punishing) or its evaluative context (e.g. annoying). There are many other measures that emphasise different aspects of pain.





Measuring potential impact of beliefs and thoughts


The importance of evaluation of the threat to body tissue has been mentioned earlier. Inherent to this evaluation is fear of movement and (re)injury. A large amount of research has investigated the role of pain-related fear avoidance behaviour. There are many specific findings that relate fear and catastrophic thought processes to pain intensity, disability and self-efficacy but the principle can be summarised thus: people who have heightened concerns about pain, its cause and its consequences, often have a sense of helplessness and adopt a passive coping style. As a result, they have a lower criterion for a movement or activity to be considered potentially painful or potentially injurious. They therefore avoid those movements and activities – ‘fear-avoidance’. Avoidance of activity leads to disuse and hampers healing and recovery, leaving the person in a vicious cycle of progressive depression, disuse and disability (Figure 17.3). According to the fear-avoidance model, most people do not follow this path because they have a more accurate and appropriate level of concern and thus do not tend to avoid movement and activity (Vlaeyen and Linton, 2000). See Vlaeyen and Linton (2000) for a review of fear-avoidance beliefs and pain and Sullivan et al. (2001) for a review of catastrophic thought processes and pain.


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Jan 7, 2017 | Posted by in PHYSICAL MEDICINE & REHABILITATION | Comments Off on Pain

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