Pain Management
REVIEW
Fear and anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance Monika I Hasenbring*,1, Omar Chehadi1, Christina Titze1 & Nina Kreddig1 Practice points ●●
Fear and anxiety are common responses to pain in daily life and play a significant role in the transition between acute and chronic pain.
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Extensive research supported the concepts of a fear–avoidance pathway that included disability as the primary outcome.
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Recent findings support the existence of additional pathways that include thought
suppression and task persistence, despite the experience of pain, fear and anxiety as important mediators in the development of chronic pain and disability. ●●
The integration of the mechanisms of associative learning, motivation and emotion
regulation helps researchers to understand how and why individuals might respond with rigid and extensive avoidance or endurance that increases the risk of long-term suffering. ●●
By considering the neurobiological concept of a phase 2 persistent pain, which is
reversible to a certain degree due to ongoing or repetitive peripheral input, opens new targets of early pharmacological and non-pharmacological strategies of pain management.
SUMMARY Substantial evidence reveals that the fear of pain and pain anxiety play a significant role in the development of chronic pain and disability, although underlying mechanisms remain widely unknown. Recent studies indicate that endurance pain responses are important besides avoidance. The purpose of this brief narrative review is to provide an overview of research that argues for the integration of the mechanisms of associative learning, motivation and emotion regulation in order to understand the questions of how and why individuals respond with pain responses, which lead to long-term suffering. By using the avoidance–endurance model of pain, we provide a concept that elucidates a range of responses to pain, fear and anxiety that mediate the transition from acute to chronic pain.
KEYWORDS
• anxiety • avoidance • endurance • fear • goal pursuit • stages of pain • thought suppression
The definition of pain as ‘an unpleasant sensory and emotional experience associated with actual or potential damage, or described in terms of such damage’ [1] , refers to complex interrelations between real or potential damage, the experience of pain and emotional responses, such as fear and anxiety. Pain-related fear may occur, for example, as an emotional response to actual damage (see for illustration Box 1, Part 1). Department of Medical Psychology & Medical Sociology, Faculty of Medicine, Ruhr-University of Bochum, Germany *Author for correspondence: [email protected] 1
10.2217/PMT.14.36 © 2014 Future Medicine Ltd
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Review Hasenbring, Chehadi, Titze & Kreddig Box 1. Two patients (names changed) from the outpatient clinic of the Department of Medical Psychology, Ruhr-University of Bochum, Germany. Part 1 We provide information about two male patients (Paul, 44 and Sam, 46). Paul has worked as a construction worker for many years, and Sam has worked as a truck driver for many years. Two years ago, both suffered from slight back pain for a few days each year. They reported feeling severe back pain that radiated to the knee for the first time during a typical situation in daily life, when they were working in their garden. Both men were heavily frightened and said, ‘How terrible, what’s that? Why just now of all times?’ Part 2 Paul continued to garden despite his fear and despite the fact that he may hurt himself again, because he was afraid to not finish his garden work on time. In the short term, he effectively managed his pain by cheering himself up and by thinking encouraging thoughts, such as ‘You’ll manage it: try to think of other things!’ However, with some delay, he began to suffer from severe pain in the evening, when he was sitting and relaxed while watching TV. Over the following weeks, he was proud to finish his gardening successfully. However, he began to suffer from severe back pain at work. He declined the recommendation of his GP to stay home for a week because he was afraid of facing negative responses at work. By contrast, Sam avoided further gardening as often as possible. He, in the short term, enjoyed the reduction of pain. Later on, he was highly disappointed that the garden was not ready to plant vegetables and flowers. He followed the recommendation of his GP to stay home for a week. Due to recurrent pain and an increase in his fear of injury, Sam took more than 6 weeks off work. He then avoided all activities that were associated with back pain, such as walking, cycling, car driving and household activities. He returned to work for weeks, but his phases of pain that required him to take and off work developed more often and for longer periods of time. Part 3 We are reminded of Sam, the truck driver. Over time, he disliked his job more and more due to his high level of stress and forced mobility. Avoidance of work on certain days due to his pain led to a reduction of his fear of pain and to relief from his distress that was caused by his expectation of having long truck drives. When he was referred to our outpatient clinic, he reported being out of work for 10 months and having an overall duration of recurrent pain of 3 years, with ongoing pain being experienced for the last 10 months. In his psychological assessment, he had elevated scores on the pain-response scales of ‘Catastrophizing’, ‘Helplessness/hopelessness’, and ‘Avoidance Behavior’ and the signs of moderate depression in the Beck Depression Inventory. Part 4 Paul liked his job: however, he increasingly suffered from recurrent episodes of pain. At work, he mostly tried to suppress thoughts and feelings about his pain and to persist in all the activities and movements that were required at his work place and in his leisure time. However, during leisure time, he more and more often had to interrupt physical activities and movements when the pain hurt too much. He increasingly felt helpless and hopeless. When he was referred to our outpatient clinic, he reported being out of work for 4 weeks, for the first time in his life. His overall duration of recurrent pain was approximately 4 years with ongoing pain being experienced over the past 2 months. In the psychological assessment, he had elevated scores in the pain-response scales ‘Helplessness/ Hopelessness’, ‘Thought Suppression’ and ‘Behavioral Endurance due to severe pain’ and the signs of mild depression in the Beck Depression Inventory.
Fear is also an emotional response to potential damage, which is elicited by stimuli that indicate possible injury and pain [2] . Anxiety may related to the possible consequences of activities that are experienced in daily life. Finally, fear and anxiety can act as precursors of future pain, that are mediated, for instance, by suboptimal motor control [3,4] . How will both men respond to their pain, fear and anxiety (see Box 1, Part 2)?
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There is ample evidence that fear of pain and pain anxiety play a significant role in the development of chronic pain and disability [5] . However, the complex mechanisms between pain, fear and anxiety, cognitions and behaviors and the resulting pain disability remain widely unresolved [6] . By using the input from psychopathological concepts over the last two decades [7–9] , several fear–avoidance models (FAM) (see Figure 1) have been developed, stimulating broad clinical and
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Fear & anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance
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Injury Disuse depression disability
Recovery
Avoidance hypervigilance Confrontation
Pain experience Pain-related fear
Pain catastrophizing
No fear
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Figure 1. Fear–avoidance model of chronic musculoskeletal pain. Reproduced with permission of the International Association for the Study of Pain (IASP) [2]. The figure may not be reproduced for any other purpose without permission.
experimental research [10,11,19,38] . The FAM suggests that in the case of acute pain, some individuals tend to interpret this sensory experience as harmful (catastrophizing), which elicits a fear of pain and/or pain-related movements. Elevated fear, in turn, activates escape from and/or avoidance of potential harmful movements and activities. In the long-term, pain disability develops as a consequence of physical disuse [2,10,11] . There is substantial evidence that supports the intertwined nature of the fear of pain, catastrophic cognitions, an exaggerated perception of pain (hypervigilance), the maintenance of pain and self-reported disability [2,10–12] . For example, a recent meta-analysis of 46 independent samples of more than 9000 patients revealed a clear and robust positive correlation between pain-related fear and disability [6] . However, several reviews referred to empirical findings that were not compatible with the sequential relationship of the variables proposed in the fear–avoidance pathway [6,13,15–19] . More specifically, the causality of the link between pain-related fear and avoidance as well as the link between catastrophizing and fear on the one hand, and disuse on the other hand, is increasingly questioned [6,13] .
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For example, in a recent review, Asmundson et al. [6] reported that five out of 13 studies (published between 1996 and 2010), which used structural equation or regression modeling in order to elucidate causal pathways that are proposed in the FAM, found conflicting or negative results. Particularly, the link between the variables of pain-related fear and escape/avoidance of physical activity was not supported. In a systematic review of nine prospective trials in regard to low back pain, which were published between 2001 and 2006, Pincus and colleagues [13] questioned the causal link between fear and avoidance, and found that fear, as well as emotional states (such as depression) are associated with inactivity. Others raise the question of whether fear may lead to alternative responses. For example, endurance coping, (i.e., cognitive/affective and behavioral responses to pain that are activated in order for a person to be able to persist in valued activities) may occur even despite severe pain, fear and anxiety. Hasenbring and colleagues [14] identified a specific subgroup of patients with subacute low back pain, who demonstrated thought suppression and task persistence also in addition to pain anxiety. Thought suppression refers to the
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Review Hasenbring, Chehadi, Titze & Kreddig automatic cognitive attempts that a person uses in order to remove unwanted emotions or sensations from awareness [15] . Task persistence, a behavioral response to pain, is defined as dysfunctional when it appears while the person is experiencing severe pain and/or pain-related fear [15] . Prospectively, these patients displayed lower recovery rates than patients who were classified as adaptive. These research findings suggest the need for an extension of modeling that considers dysfunctional variables that are not found in fear–avoidance pathways [6,13,15–18] . Among different theoretical approaches that have been reviewed during the past 5 years [19–25] , the avoidance–endurance model (AEM) [15,26] of pain, as well as the concepts of neurophysiology, associative learning, motivation and emotion regulation, are proposed in this brief review, which focuses on the exploration of and explanations related to different pathways in the transition from acute to chronic pain. Brief outline of the avoidance–endurance model The core component of the AEM is the assumption that people who experience pain reveal
characteristic patterns of cognitive, affective and behavioral responses to that pain, which influence maintenance of pain and disability (see Figure 2) . Patients with a fear–avoidance response pattern (FAR) repeatedly respond with elevated fear, catastrophizing, helplessness and escape/avoidance behaviors. They run the risk of developing inactivity and signs of disuse due to reduced musculoskeletal and cardiovascular fitness in the long term [27] . In this respect, the FAR pathway is conceptualized as identical to the FAM pathway that is proposed by Vlaeyen and Linton [2,19] . In contrast to the FAM, the AEM proposes further dysfunctional pathways that contribute to the development of chronic pain. The AEM suggests that there are people who respond to pain with anxiety and/or depression, thought suppression, and who respond to the severe pain behaviorally with persistence in physical and social activities (distress-endurance responses [DER]). Due to maladaptive emotion processing, DER patients face the risk of developing increased emotional distress in the short term. Task persistence is suggested to cause suboptimal motor control and tissue loading [3,4] ,
Acute Pain
Catastrophizing
Thought Suppression
Distraction/Ignoring
Fear/Anxiety
Anxiety/Depressive Mood
Positive Mood
Avoidance Behavior
Endurance Behavior
Endurance Behavior
Muscular Insufficiency
Muscular Overload
Muscular Overload
Development CLBP
Development CLBP
Development CLBP
Reduction of Pain
EER
AR
FAR
DER
Coping Signal
Flexible Balance Avoidance/Endurance
Avoidance–Endurance Model
Figure 2. Avoidance-endurance Model of Pain. Avoidance-endurance model elucidating several pathways from acute to chronic musculoskeletal pain versus an adaptive pain response pattern. AR: Adaptive pain responses; CLBP: Chronic low back pain; DER: Distress-endurance responses; EER: Eustress-endurance responses; FAR: Fear avoidance responses.
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Fear & anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance which can lead to the maintenance of pain and disability in the long term. Further, individuals who respond to pain with focused distraction, positive mood despite pain and task persistence are classified as eustress–endurance responders (EER). These patients seem to recover from pain disorders in the short-term and, develop increased pain in the long-term [28] . A fourth pattern suggested that patients who respond to pain with a flexible change between shortterm avoidance and endurance, experience appropriate recovery in the long-term (adaptive pain responses [AR]) [14] . The adaptive pattern shares a number of features with the pattern of confrontation, which was proposed as a functional response to pain in several versions of the FAM [2,6,10,11,17–19,38] . Current research focuses on the question of how these responses may lead to the maintenance or recurrence of pain and/or disability, and elucidates possible neurocognitive/affective, and neurobehavioral mechanisms in the pathway from acute to chronic pain [29] . Due to some of these response patterns being unexpected at first glance, we further need to answer the question of why some people respond to pain with maladaptive pain responses that yield the long-term consequences of ongoing pain and disability. We integrate some basic issues that come from more recent developments in psychology, psychopathology and neuroscience. We refer to the differentiation of pain stages that are due to neurophysiological mechanisms, the differentiation of fear and anxiety and the role of motivation, emotion processing and learning in adaptive and maladaptive pathways. Impact from neurobiology: there are different stages of pain The likelihood of determining whether an experience of pain signals real or potential physical damage or whether this signal is ‘useless’ depends largely on the characteristics of time and the situation. In neurophysiology, acute pain (i.e., heat stimulation in the lab or an acute phase of back pain where a noxious stimulus is identifiable), is labeled as phase 1 pain [30] , nociceptive pain or the phase of activation of the pain system [31] . A basic hardwired route of the transmission between the periphery via the spinal cord, the thalamus and the cortex results in a close correlation between discharges of peripheral nociceptors and the subjective experience of the sensory aspects of pain, such as localization
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and the duration of the stimulus [30] . Complete reversibility is an important characteristic of phase 1 pain. Phase 2 pain is characterized by peripheral tissue damage and signs of inflammation, with the latter being part of the normal healing process [30] . Tissue damage and inflammation, in turn, modulate the response characteristics of the various components of the nociceptive system which leads to different types of peripheral sensitization [32] . Response thresholds for the excitation of nociceptors may be decreased and ‘sleepy’ nociceptors are excitable in the condition of inflammation [32] . These peripheral processes of modulation cause a change in neuronal responsiveness when the stimulation ends (maintenance over time) or when following a low-level peripheral input (generalization in regard to low-level stimuli) [31] . Processes of pain modulation are suggested to be reversible: ‘as healing progresses, recovery to the phase 1 state will occur, and, thus, the system will restore its balance in the long term’ [30 p 271]. Finally, phase 3 of ‘abnormal’ or chronic pain was described, to be characterized by signs of spontaneous pain, very low pain thresholds and mechanical allodynia [30] . Processes of altered gene regulation, loss of inhibitory neurons and cell death contribute to this stage of modification [31] which seems to be difficult to reverse. As these processes of peripheral and central sensitization proceed, pain increasingly loses its ability to be a warning signal of real tissue damage [1] . However, especially in patients who are suffering from chronic musculoskeletal disorders, such as widespread pain or chronic neck pain, research has demonstrated that altered central processing may be maintained dynamically by peripheral input. For instance, microdialysis as a technique that assesses the biochemical interstitial milieu of a tissue or increased interstitial concentrations of algesic substances (such as lactate, pyruvate, and/or glutamate) has been shown in the trapezius muscles of patients who suffer from chronic neck pain and in patients with chronic widespread pain, such as fibromyalgia [33] . These are alterations that may be, at least partially, reversible even in the chronic phases of pain [34] . Thus, in phase 2 and even in certain chronic pain states it is difficult to determine whether pain holds its warning function or not. This type of uncertainty characterizes sub-acute and
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Review Hasenbring, Chehadi, Titze & Kreddig chronic phases of pain [35] , which may cause fear and/or anxiety in patients and in health care providers [36,37] . Fear & anxiety & their relationship to different sources of threat In their reformulation of the fear–avoidance model, Gordon Asmundson and colleagues introduced the differentiation between the emotional states of fear and anxiety in pain research [38] . Although fear and anxiety share a number of physiological, cognitive and behavioral features, they also seem to be distinct in certain respects. Theories and experimental research that range from ethoexperimental animal approaches [39] , and, ethopharmacological research [40] to appraisal theories [41] and neuroscience [42,43] , delivered concepts that had a stronger focus on the distinct features of fear and anxiety [44] . A central message in this research is that fear and anxiety may be able to be distinguished by using two characteristics of a situation: the ‘defensive direction’ and the ‘defensive distance’ [44] . In regard to defensive direction, fear as a phasic response is elicited by a confrontation with a threatening stimulus, which motivates the animal or human to move away from this type of danger, if possible, and activates the flight/fight/ freezing system. In contrast, anxiety will be elicited when the animal or human approaches a potential threat and the approach behavior via the behavioral approach system is motivated by a specific reward or the omission of punishment. Anxiety may be a more tonic reaction to conflicts between competing goals [40] that are detected by a third neural system, the behavioral inhibition system. Behavioral responses depend on the distance of the danger, and whether avoidance seems possible. In the case of direct confrontation with a threatening stimulus that is avoidable, fear motivates the behavioral responses of active avoidance or defensive avoidance behaviors. If the threatening object is not avoidable, responses of high intensive fear (panic), fight or freezing may be more likely. In the case of approaching a future potential threat that is avoidable, resulting anxiety will lead to certain behavioral responses such as increased risk assessment and passive avoidance (defensive approach behaviors), where the tendency to approach the conflicting goal is blocked [45] . Based primarily on animal research, fear and anxiety are shown to be related to different neural regions [39] . Whereas fear and defensive
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avoidance are related to changes in the activity of the anterior cingulate cortex and amygdala, anxiety and defensive approach behaviors, are related to the posterior cingulate and the septohippocampal system [40] which also plays a significant role in memory function. Research has validated these associations by showing that anxiety and risk assessment are sensitive to classical anxiolytic drugs, such as barbiturates or benzodiazepines, while fear and active avoidance are not sensitive to these drugs. By using imaging of brain activation in humans, Ochsner and colleagues identified different neural systems that are activated by fear and anxiety. Anxiety, due to the possible negative implications of physical sensations, predicted activation of a medial prefrontal region that is associated with self-focused attention and goal pursuit. In contrast, fear of pain was associated with the activation of the anterior and posterior cingulate regions that are related to monitoring and evaluating affective responses [42] . The differentiation between fear and anxiety also has a parallel in factor-analytic approaches of self-report data [46] . The authors demonstrated that scales that assess fear-related constructs are represented on a separate dimension, whereas scales that measure pain-related anxiety are represented on the dimension ‘cognitive intrusion by pain’, which refers to a person’s characteristics of worrying. The AEM suggests that fear and active escape/avoidance are more pronounced in the fear–avoidance pathway and that painanxiety and different types of passive avoidance besides endurance are characteristic of the distress–endurance pattern [28] . Motivation & learning I: the adaptive function of pain, fear & anxiety – avoidance in the face of danger is easy to comprehend, but persistence in this situation is not easy to understand Emotions, such as fear and anxiety, may serve as the coordinates of physiological, cognitive, motivational, and behavioral responses in patterns that increase one’s ability to meet the adaptive challenges of situations [47] . In comparison, pain serves as a signal of the actual or possible threat of body damage in order to motivate protective behaviors [30] . Research on pain and emotional processing has a long tradition of exploring the role of the mechanisms of associative learning in the generalization of pain and fear to situations that are not innately
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Fear & anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance causal. Due to the processes of classical conditioning, a behavioral response to pain will be elicited over time by numerous external and internal stimuli [19] that occurred shortly before the original stimulus occurred. In the case of real harm, this situation may be adaptive, which Nesse and Ellsworth noted by stating that ‘fear two seconds before a danger is far better than two seconds after’ [47 p.132], in stimulating protective behaviors. Situational cues, such as discriminative stimuli, inform the individual about the possible outcomes of a specific behavior, including whether escape will lead to pain reduction, or whether a situation, in general, allows escape/avoidance [48] . Persistence in an activity despite experiencing severe pain, fear or anxiety represents a fight response that is a substantial part of the flight/fight/freezing system [40] . Research in animals is mostly concerned with the effects of the flight or freezing responses. When using mice and cats, this may be plausible because flight would be the most adaptive strategy when escape is possible, while freezing would occur when there is no way to escape. Fighting would lead to death in animals. In humans, most pain situations allow certain types of fighting such as the maintenance of a certain activity despite experiencing pain. There is ample evidence that persistence behavior, despite the presence of elevated pain, is reported to occur equally as or even more often than avoidance in patients who suffer from back pain [20,49–51] . When & why do we fight in the face of danger? Fight or flight responses (escape or persistence) when pain and fear signal threat, imply that making a decision between these responses is possible. Research on motivation and goaldirected behavior has introduced this perspective in pain research [52–55] . Individual goal conflicts besides pain severity have an impact on pain anxiety, which in turn, mediates the effects of pain on disability [53] . In daily life, pain normally interrupts ongoing activities [54] , which requires activation of goal-directed behavior and enables an individual to realize that there is a context-sensitive balance between these antagonistic challenges [56] . Effective goal shielding increases task persistence, which is mediated by certain moderator variables, such as individuals’ level of commitment to a goal, their goal-related tenacity and
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the degree of anxiety and depression [57] . In an elegant experiment, Crombez and colleagues [58] demonstrated that healthy volunteers reported higher effort in order to persist in a cognitive task when they were confronted with a pain stimulus. Moreover, Rachman [59] argued in an interesting monograph, that people persist in threatening activities despite fear, when a specific motivation or commitment, drives these activities. How do we respond to danger? The role of emotion regulation Emotion regulation, by which humans modify the onset or the outcomes of emotions, encompasses a broad set of conscious and non-volitional cognitive, physiological and behavioral responses [60] . Cognitive processing, including attention direction toward or away from a threatening stimulus and the appraisal of a situation play a significant role in one’s resulting emotional state. Research in attention direction has a long tradition in using experimental pain research [61,62] . Focused distraction as a strategy to direct attention away from a threatening pain stimulus to a distracting stimulus has been shown to reduce pain sensitivity and increase pain tolerance [61,62] . However, similar effects have been shown in regard to monitoring the sensory sensations of pain [63] . In contrast, different types of unfocused distraction, where people are instructed to suppress their thoughts about pain or unwanted thoughts, yielded less conclusive results. Thought suppression also led to attention diversion but revealed a high percentage of failures [64] . Interestingly, most people prefer distraction from pain to pain monitoring [62] , and, even in regard to chronic pain thought suppression appeared to be reported most often [14,28,49] . Modern appraisal theories specify certain characteristics of situations that matter for survival, well-being and success in attaining goals [47,65,66] . An individual’s appraisal of situations that produce novelty, unpredictability, or goal obstacles plays a significant role in emotion processing including one’s awareness of emotions and their regulation. In the context of pain, fear and anxiety, there is substantial evidence that reappraisal and acceptance of feelings of distress represent adaptive forms of cognitive emotion regulation [41,67–69] . In contrast, interpreting a pain stimulus to be highly threatening appears
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Review Hasenbring, Chehadi, Titze & Kreddig to be dysfunctional when there is no real threat or when the threat of pain is overinterpreted [70] . However, there is no doubt that appraisal of real danger as threatening may increase the efficacy of the warning signal function. Motivation & learning II: when pain, fear & anxiety turn into maladaptivity Due to their functions as signals that indicate possible threat, pain, fear and anxiety should continue to be seen as transient states of arousal. Maladaptivity in regard to these responses may occur in the following three conditions: first, when these states are elicited in situations where no real threat is present (generalization over situations); second, when the time needed for the solution of the problem, such as healing time, is excessive (maintenance over time); third, when intensity exceeds (situational amplification) or falls below a certain level where coordinated action is not possible. The impairment or loss of the warning function leads to detrimental effects such as a delay in wound healing [71] or a reduction in life expectancy in patients with congenital insensitivity to pain [72] . Generalization over situations and maintenance over time, when no real threat of physical damage is detectable, can be explained by using a combination of the theories of learning, motivation, and emotion processing. Due to substantial work by Fordyce [48] , who explored the role of associative learning in the maintenance of fear and pain, we know that avoidance behavior often becomes a stable response, even when real physical danger is not present. Avoidance may be negatively reinforced when it effectively reduces the fear of pain or of pain-irrelevant distress (see for illustration Box 1, Part 3). In terms of goal pursuit theory, Sam was in a situation of goal facilitation, where one goal (e.g. to avoid of stress at work) effectively was pursued by another goal (avoidance of pain due to long truck drives) [73] . In terms of learning theory, avoidance behavior becomes functional in regard to other goals besides pain [10,11,48] . Furthermore, predispositional factors, such as high levels of anxiety sensitivity or environmental stress, are shown to increase one’s likelihood of developing conditioned responses to fear and associated avoidance [16,38,74] . In contrast to avoidance, persistence despite pain becomes maladaptive if the pain signals real physical harm. Causing physical damage when persisting in repetitive or ongoing activities
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may be likely in regard to activity-dependent pain [30,31] , where the processes of healing after acute damage should be allowed to occur. As described above, uncertainty exists in regard to the presence of real physical danger, which causes a certain degree of anxiety. Preliminary narrative [15] and systematic reviews [75] revealed positive cross-sectional associations between pain persistence and the intensity of back pain. As reported above, persistence and anxiety was shown in a specific subgroup of patients with subacute low back pain, who displayed a DER pattern [14] . In several prospective studies, DER patients have been shown to have maladaptive strategies in terms of pain and disability in the long term [14,28,76] . By measuring accelerometer-based physical activity, research found that these patients demonstrated the highest levels of specific strain postures despite experiencing pain [20,21] , which presumably led to a suboptimal pattern of motor control and real physical damage [4] . In the short term, persistence despite pain is suggested to be maintained by the mechanisms of operant learning. Persistence in a pain-irrelevant task despite the experience of pain may lead to an increase in pain tolerance, which facilitates the pursuit of pain-irrelevant goals [77–80] . The reduction of pain, the increase of tolerance and the successful pursuit of painirrelevant goals serve as reinforcing stimuli that are known to stabilize relevant behavior. In the long term, persistence despite severe pain, may lead to ongoing or repetitive overuse/overload of physical structures, such as muscles or discs, which may lead to and maintain chronic states of pain and disability (see the illustration in Box 1, Part 4) [3,4,20,21,33] . Amplification of pain, fear and anxiety involves conscious and non-volitional interpretations of a pain stimulus as highly threatening (catastrophizing) and attention direction towards the threatening aspects of pain (hypervigilance) [81,82] . The tendency to evaluate a pain stimulus, which is caused for example, by a slight transient biomechanical load, as highly threatening (‘Do I have a fracture?’), may initiate a circuit of feedback mechanisms, that elicit fear and increased physiological arousal, which, in turn, serves as a stimulus that intensifies the threatening appraisal (‘There must be a fracture! It would be a catastrophe if I had to interrupt my work!’) [83,84] . In the fear-avoidance pathway, individuals are suggested to volitionally check the surroundings in order to effectively avoid future threats.
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Fear & anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance A more non-volitional mode of hypervigilance was suggested as part of a paradoxical response to the cognitive suppression of pain, fear or anxiety (‘Do not think about your pain!’). There is substantial evidence from experimental research that these attempts to remove unwanted thoughts from awareness often fail. Moreover, a rebound phenomenon was observed that led to a nonvolitional increase in attention direction towards unwanted feelings and thoughts [85,86] that may lead to the maintenance of anxiety or pain. This increased attention to unwanted thoughts may reflect a non-volitional, automatic type of attention direction, that appears as ‘amplification’ or ‘non-volitional hypervigilance’ [85,86] . A recent meta-analysis on emotion regulation in affective disorders provided substantial evidence for the positive associations between thought suppression and anxiety disorders [67] . In regard to pain, experimental research indicated paradoxical increases of pain and distress that were caused by the instruction to suppress thoughts about pain during a painful stimulation [77–79] . In sum, processes of emotion regulation and goal pursuit that are automatic or more deliberate, work in concert with processes of associative learning that lead to maladaptive forms of pain, fear, and anxiety. This maladaptivity occurs when pain is generalized over many situations that are not innately threatening, in the case of maintenance over normal healing time and in the case of dysfunctional amplification. Especially in the phase of subacute pain, one of the most crucial challenges is to determine whether a pain stimulus signals real or potential physical damage or not and to decide, how to evaluate the severity of this damage and handle high levels of uncertainty. Conclusion & future perspective There is substantial evidence that fear and anxiety, common responses to pain in daily life, play a significant role in the transition between acute and chronic pain. While extensive research has References Papers of special note have been highlighted as: • of interest 1
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Task Force on Taxonomy of the International Association for the Study of Pain. Merskey H, Bogduk N. (Eds). IASP Press, WA, USA (1994). Vlaeyen JW, Linton SJ. Fear-avoidance and its consequences in chronic musculoskeletal
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supported the concepts of a fear–avoidance pathway, recent findings support the existence of additional pathways that include elevated endurance coping as an important mediator in the development of chronic pain and disability. Most evidence is reported in the field of nonspecific low back pain, although pain persistence has already been described in regard to different pain disorders, such as fibromyalgia [87] or sciatic pain [28,76,88] . These findings demonstrate that there is no causal link between pain-related fear/ anxiety and avoidance behavior. Instead, under some circumstances, endurance coping may be an alternative response to pain or fear/anxiety. Over the next 5 to 10 years, the integration of the mechanisms of associative learning, motivation and emotion regulation will help researchers to understand the questions of how and why individuals might respond with rigid and extensive avoidance or endurance that increases the risk of long-term suffering. The AEM provides extensions of the fear–avoidance pathway that elucidate pain responses such as thought suppression and task persistence despite the experience of severe pain and even despite experiencing fear and anxiety. These concepts deliver evidence that is based on the rationale regarding individually targeted strategies of pain management that include more effective patient reassurance [89] and cognitive-behavioral treatments [90] . Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Writing assistance was utilized in the production of this manuscript. The manuscript was edited by American Journal Experts with the costs covered by the authors’ department (Department of Medical Psychology & Medical Sociology, Ruhr-University of Bochum). existing theories. Changes at multiple levels of the nervous system are reviewed introducing the distinction between short term benefits (e.g., protection of the injured and painful part) and long term consequences (e.g., an increase of load and decrease of movement).
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REVIEW
Fear and anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance Monika I Hasenbring*,1, Omar Chehadi1, Christina Titze1 & Nina Kreddig1 Practice points ●●
Fear and anxiety are common responses to pain in daily life and play a significant role in the transition between acute and chronic pain.
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Extensive research supported the concepts of a fear–avoidance pathway that included disability as the primary outcome.
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Recent findings support the existence of additional pathways that include thought
suppression and task persistence, despite the experience of pain, fear and anxiety as important mediators in the development of chronic pain and disability. ●●
The integration of the mechanisms of associative learning, motivation and emotion
regulation helps researchers to understand how and why individuals might respond with rigid and extensive avoidance or endurance that increases the risk of long-term suffering. ●●
By considering the neurobiological concept of a phase 2 persistent pain, which is
reversible to a certain degree due to ongoing or repetitive peripheral input, opens new targets of early pharmacological and non-pharmacological strategies of pain management.
SUMMARY Substantial evidence reveals that the fear of pain and pain anxiety play a significant role in the development of chronic pain and disability, although underlying mechanisms remain widely unknown. Recent studies indicate that endurance pain responses are important besides avoidance. The purpose of this brief narrative review is to provide an overview of research that argues for the integration of the mechanisms of associative learning, motivation and emotion regulation in order to understand the questions of how and why individuals respond with pain responses, which lead to long-term suffering. By using the avoidance–endurance model of pain, we provide a concept that elucidates a range of responses to pain, fear and anxiety that mediate the transition from acute to chronic pain.
KEYWORDS
• anxiety • avoidance • endurance • fear • goal pursuit • stages of pain • thought suppression
The definition of pain as ‘an unpleasant sensory and emotional experience associated with actual or potential damage, or described in terms of such damage’ [1] , refers to complex interrelations between real or potential damage, the experience of pain and emotional responses, such as fear and anxiety. Pain-related fear may occur, for example, as an emotional response to actual damage (see for illustration Box 1, Part 1). Department of Medical Psychology & Medical Sociology, Faculty of Medicine, Ruhr-University of Bochum, Germany *Author for correspondence: [email protected] 1
10.2217/PMT.14.36 © 2014 Future Medicine Ltd
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part of
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Review Hasenbring, Chehadi, Titze & Kreddig Box 1. Two patients (names changed) from the outpatient clinic of the Department of Medical Psychology, Ruhr-University of Bochum, Germany. Part 1 We provide information about two male patients (Paul, 44 and Sam, 46). Paul has worked as a construction worker for many years, and Sam has worked as a truck driver for many years. Two years ago, both suffered from slight back pain for a few days each year. They reported feeling severe back pain that radiated to the knee for the first time during a typical situation in daily life, when they were working in their garden. Both men were heavily frightened and said, ‘How terrible, what’s that? Why just now of all times?’ Part 2 Paul continued to garden despite his fear and despite the fact that he may hurt himself again, because he was afraid to not finish his garden work on time. In the short term, he effectively managed his pain by cheering himself up and by thinking encouraging thoughts, such as ‘You’ll manage it: try to think of other things!’ However, with some delay, he began to suffer from severe pain in the evening, when he was sitting and relaxed while watching TV. Over the following weeks, he was proud to finish his gardening successfully. However, he began to suffer from severe back pain at work. He declined the recommendation of his GP to stay home for a week because he was afraid of facing negative responses at work. By contrast, Sam avoided further gardening as often as possible. He, in the short term, enjoyed the reduction of pain. Later on, he was highly disappointed that the garden was not ready to plant vegetables and flowers. He followed the recommendation of his GP to stay home for a week. Due to recurrent pain and an increase in his fear of injury, Sam took more than 6 weeks off work. He then avoided all activities that were associated with back pain, such as walking, cycling, car driving and household activities. He returned to work for weeks, but his phases of pain that required him to take and off work developed more often and for longer periods of time. Part 3 We are reminded of Sam, the truck driver. Over time, he disliked his job more and more due to his high level of stress and forced mobility. Avoidance of work on certain days due to his pain led to a reduction of his fear of pain and to relief from his distress that was caused by his expectation of having long truck drives. When he was referred to our outpatient clinic, he reported being out of work for 10 months and having an overall duration of recurrent pain of 3 years, with ongoing pain being experienced for the last 10 months. In his psychological assessment, he had elevated scores on the pain-response scales of ‘Catastrophizing’, ‘Helplessness/hopelessness’, and ‘Avoidance Behavior’ and the signs of moderate depression in the Beck Depression Inventory. Part 4 Paul liked his job: however, he increasingly suffered from recurrent episodes of pain. At work, he mostly tried to suppress thoughts and feelings about his pain and to persist in all the activities and movements that were required at his work place and in his leisure time. However, during leisure time, he more and more often had to interrupt physical activities and movements when the pain hurt too much. He increasingly felt helpless and hopeless. When he was referred to our outpatient clinic, he reported being out of work for 4 weeks, for the first time in his life. His overall duration of recurrent pain was approximately 4 years with ongoing pain being experienced over the past 2 months. In the psychological assessment, he had elevated scores in the pain-response scales ‘Helplessness/ Hopelessness’, ‘Thought Suppression’ and ‘Behavioral Endurance due to severe pain’ and the signs of mild depression in the Beck Depression Inventory.
Fear is also an emotional response to potential damage, which is elicited by stimuli that indicate possible injury and pain [2] . Anxiety may related to the possible consequences of activities that are experienced in daily life. Finally, fear and anxiety can act as precursors of future pain, that are mediated, for instance, by suboptimal motor control [3,4] . How will both men respond to their pain, fear and anxiety (see Box 1, Part 2)?
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There is ample evidence that fear of pain and pain anxiety play a significant role in the development of chronic pain and disability [5] . However, the complex mechanisms between pain, fear and anxiety, cognitions and behaviors and the resulting pain disability remain widely unresolved [6] . By using the input from psychopathological concepts over the last two decades [7–9] , several fear–avoidance models (FAM) (see Figure 1) have been developed, stimulating broad clinical and
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Fear & anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance
Review
Injury Disuse depression disability
Recovery
Avoidance hypervigilance Confrontation
Pain experience Pain-related fear
Pain catastrophizing
No fear
Negative affectivity threatening illness information
Figure 1. Fear–avoidance model of chronic musculoskeletal pain. Reproduced with permission of the International Association for the Study of Pain (IASP) [2]. The figure may not be reproduced for any other purpose without permission.
experimental research [10,11,19,38] . The FAM suggests that in the case of acute pain, some individuals tend to interpret this sensory experience as harmful (catastrophizing), which elicits a fear of pain and/or pain-related movements. Elevated fear, in turn, activates escape from and/or avoidance of potential harmful movements and activities. In the long-term, pain disability develops as a consequence of physical disuse [2,10,11] . There is substantial evidence that supports the intertwined nature of the fear of pain, catastrophic cognitions, an exaggerated perception of pain (hypervigilance), the maintenance of pain and self-reported disability [2,10–12] . For example, a recent meta-analysis of 46 independent samples of more than 9000 patients revealed a clear and robust positive correlation between pain-related fear and disability [6] . However, several reviews referred to empirical findings that were not compatible with the sequential relationship of the variables proposed in the fear–avoidance pathway [6,13,15–19] . More specifically, the causality of the link between pain-related fear and avoidance as well as the link between catastrophizing and fear on the one hand, and disuse on the other hand, is increasingly questioned [6,13] .
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For example, in a recent review, Asmundson et al. [6] reported that five out of 13 studies (published between 1996 and 2010), which used structural equation or regression modeling in order to elucidate causal pathways that are proposed in the FAM, found conflicting or negative results. Particularly, the link between the variables of pain-related fear and escape/avoidance of physical activity was not supported. In a systematic review of nine prospective trials in regard to low back pain, which were published between 2001 and 2006, Pincus and colleagues [13] questioned the causal link between fear and avoidance, and found that fear, as well as emotional states (such as depression) are associated with inactivity. Others raise the question of whether fear may lead to alternative responses. For example, endurance coping, (i.e., cognitive/affective and behavioral responses to pain that are activated in order for a person to be able to persist in valued activities) may occur even despite severe pain, fear and anxiety. Hasenbring and colleagues [14] identified a specific subgroup of patients with subacute low back pain, who demonstrated thought suppression and task persistence also in addition to pain anxiety. Thought suppression refers to the
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Review Hasenbring, Chehadi, Titze & Kreddig automatic cognitive attempts that a person uses in order to remove unwanted emotions or sensations from awareness [15] . Task persistence, a behavioral response to pain, is defined as dysfunctional when it appears while the person is experiencing severe pain and/or pain-related fear [15] . Prospectively, these patients displayed lower recovery rates than patients who were classified as adaptive. These research findings suggest the need for an extension of modeling that considers dysfunctional variables that are not found in fear–avoidance pathways [6,13,15–18] . Among different theoretical approaches that have been reviewed during the past 5 years [19–25] , the avoidance–endurance model (AEM) [15,26] of pain, as well as the concepts of neurophysiology, associative learning, motivation and emotion regulation, are proposed in this brief review, which focuses on the exploration of and explanations related to different pathways in the transition from acute to chronic pain. Brief outline of the avoidance–endurance model The core component of the AEM is the assumption that people who experience pain reveal
characteristic patterns of cognitive, affective and behavioral responses to that pain, which influence maintenance of pain and disability (see Figure 2) . Patients with a fear–avoidance response pattern (FAR) repeatedly respond with elevated fear, catastrophizing, helplessness and escape/avoidance behaviors. They run the risk of developing inactivity and signs of disuse due to reduced musculoskeletal and cardiovascular fitness in the long term [27] . In this respect, the FAR pathway is conceptualized as identical to the FAM pathway that is proposed by Vlaeyen and Linton [2,19] . In contrast to the FAM, the AEM proposes further dysfunctional pathways that contribute to the development of chronic pain. The AEM suggests that there are people who respond to pain with anxiety and/or depression, thought suppression, and who respond to the severe pain behaviorally with persistence in physical and social activities (distress-endurance responses [DER]). Due to maladaptive emotion processing, DER patients face the risk of developing increased emotional distress in the short term. Task persistence is suggested to cause suboptimal motor control and tissue loading [3,4] ,
Acute Pain
Catastrophizing
Thought Suppression
Distraction/Ignoring
Fear/Anxiety
Anxiety/Depressive Mood
Positive Mood
Avoidance Behavior
Endurance Behavior
Endurance Behavior
Muscular Insufficiency
Muscular Overload
Muscular Overload
Development CLBP
Development CLBP
Development CLBP
Reduction of Pain
EER
AR
FAR
DER
Coping Signal
Flexible Balance Avoidance/Endurance
Avoidance–Endurance Model
Figure 2. Avoidance-endurance Model of Pain. Avoidance-endurance model elucidating several pathways from acute to chronic musculoskeletal pain versus an adaptive pain response pattern. AR: Adaptive pain responses; CLBP: Chronic low back pain; DER: Distress-endurance responses; EER: Eustress-endurance responses; FAR: Fear avoidance responses.
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Fear & anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance which can lead to the maintenance of pain and disability in the long term. Further, individuals who respond to pain with focused distraction, positive mood despite pain and task persistence are classified as eustress–endurance responders (EER). These patients seem to recover from pain disorders in the short-term and, develop increased pain in the long-term [28] . A fourth pattern suggested that patients who respond to pain with a flexible change between shortterm avoidance and endurance, experience appropriate recovery in the long-term (adaptive pain responses [AR]) [14] . The adaptive pattern shares a number of features with the pattern of confrontation, which was proposed as a functional response to pain in several versions of the FAM [2,6,10,11,17–19,38] . Current research focuses on the question of how these responses may lead to the maintenance or recurrence of pain and/or disability, and elucidates possible neurocognitive/affective, and neurobehavioral mechanisms in the pathway from acute to chronic pain [29] . Due to some of these response patterns being unexpected at first glance, we further need to answer the question of why some people respond to pain with maladaptive pain responses that yield the long-term consequences of ongoing pain and disability. We integrate some basic issues that come from more recent developments in psychology, psychopathology and neuroscience. We refer to the differentiation of pain stages that are due to neurophysiological mechanisms, the differentiation of fear and anxiety and the role of motivation, emotion processing and learning in adaptive and maladaptive pathways. Impact from neurobiology: there are different stages of pain The likelihood of determining whether an experience of pain signals real or potential physical damage or whether this signal is ‘useless’ depends largely on the characteristics of time and the situation. In neurophysiology, acute pain (i.e., heat stimulation in the lab or an acute phase of back pain where a noxious stimulus is identifiable), is labeled as phase 1 pain [30] , nociceptive pain or the phase of activation of the pain system [31] . A basic hardwired route of the transmission between the periphery via the spinal cord, the thalamus and the cortex results in a close correlation between discharges of peripheral nociceptors and the subjective experience of the sensory aspects of pain, such as localization
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and the duration of the stimulus [30] . Complete reversibility is an important characteristic of phase 1 pain. Phase 2 pain is characterized by peripheral tissue damage and signs of inflammation, with the latter being part of the normal healing process [30] . Tissue damage and inflammation, in turn, modulate the response characteristics of the various components of the nociceptive system which leads to different types of peripheral sensitization [32] . Response thresholds for the excitation of nociceptors may be decreased and ‘sleepy’ nociceptors are excitable in the condition of inflammation [32] . These peripheral processes of modulation cause a change in neuronal responsiveness when the stimulation ends (maintenance over time) or when following a low-level peripheral input (generalization in regard to low-level stimuli) [31] . Processes of pain modulation are suggested to be reversible: ‘as healing progresses, recovery to the phase 1 state will occur, and, thus, the system will restore its balance in the long term’ [30 p 271]. Finally, phase 3 of ‘abnormal’ or chronic pain was described, to be characterized by signs of spontaneous pain, very low pain thresholds and mechanical allodynia [30] . Processes of altered gene regulation, loss of inhibitory neurons and cell death contribute to this stage of modification [31] which seems to be difficult to reverse. As these processes of peripheral and central sensitization proceed, pain increasingly loses its ability to be a warning signal of real tissue damage [1] . However, especially in patients who are suffering from chronic musculoskeletal disorders, such as widespread pain or chronic neck pain, research has demonstrated that altered central processing may be maintained dynamically by peripheral input. For instance, microdialysis as a technique that assesses the biochemical interstitial milieu of a tissue or increased interstitial concentrations of algesic substances (such as lactate, pyruvate, and/or glutamate) has been shown in the trapezius muscles of patients who suffer from chronic neck pain and in patients with chronic widespread pain, such as fibromyalgia [33] . These are alterations that may be, at least partially, reversible even in the chronic phases of pain [34] . Thus, in phase 2 and even in certain chronic pain states it is difficult to determine whether pain holds its warning function or not. This type of uncertainty characterizes sub-acute and
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Review Hasenbring, Chehadi, Titze & Kreddig chronic phases of pain [35] , which may cause fear and/or anxiety in patients and in health care providers [36,37] . Fear & anxiety & their relationship to different sources of threat In their reformulation of the fear–avoidance model, Gordon Asmundson and colleagues introduced the differentiation between the emotional states of fear and anxiety in pain research [38] . Although fear and anxiety share a number of physiological, cognitive and behavioral features, they also seem to be distinct in certain respects. Theories and experimental research that range from ethoexperimental animal approaches [39] , and, ethopharmacological research [40] to appraisal theories [41] and neuroscience [42,43] , delivered concepts that had a stronger focus on the distinct features of fear and anxiety [44] . A central message in this research is that fear and anxiety may be able to be distinguished by using two characteristics of a situation: the ‘defensive direction’ and the ‘defensive distance’ [44] . In regard to defensive direction, fear as a phasic response is elicited by a confrontation with a threatening stimulus, which motivates the animal or human to move away from this type of danger, if possible, and activates the flight/fight/ freezing system. In contrast, anxiety will be elicited when the animal or human approaches a potential threat and the approach behavior via the behavioral approach system is motivated by a specific reward or the omission of punishment. Anxiety may be a more tonic reaction to conflicts between competing goals [40] that are detected by a third neural system, the behavioral inhibition system. Behavioral responses depend on the distance of the danger, and whether avoidance seems possible. In the case of direct confrontation with a threatening stimulus that is avoidable, fear motivates the behavioral responses of active avoidance or defensive avoidance behaviors. If the threatening object is not avoidable, responses of high intensive fear (panic), fight or freezing may be more likely. In the case of approaching a future potential threat that is avoidable, resulting anxiety will lead to certain behavioral responses such as increased risk assessment and passive avoidance (defensive approach behaviors), where the tendency to approach the conflicting goal is blocked [45] . Based primarily on animal research, fear and anxiety are shown to be related to different neural regions [39] . Whereas fear and defensive
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avoidance are related to changes in the activity of the anterior cingulate cortex and amygdala, anxiety and defensive approach behaviors, are related to the posterior cingulate and the septohippocampal system [40] which also plays a significant role in memory function. Research has validated these associations by showing that anxiety and risk assessment are sensitive to classical anxiolytic drugs, such as barbiturates or benzodiazepines, while fear and active avoidance are not sensitive to these drugs. By using imaging of brain activation in humans, Ochsner and colleagues identified different neural systems that are activated by fear and anxiety. Anxiety, due to the possible negative implications of physical sensations, predicted activation of a medial prefrontal region that is associated with self-focused attention and goal pursuit. In contrast, fear of pain was associated with the activation of the anterior and posterior cingulate regions that are related to monitoring and evaluating affective responses [42] . The differentiation between fear and anxiety also has a parallel in factor-analytic approaches of self-report data [46] . The authors demonstrated that scales that assess fear-related constructs are represented on a separate dimension, whereas scales that measure pain-related anxiety are represented on the dimension ‘cognitive intrusion by pain’, which refers to a person’s characteristics of worrying. The AEM suggests that fear and active escape/avoidance are more pronounced in the fear–avoidance pathway and that painanxiety and different types of passive avoidance besides endurance are characteristic of the distress–endurance pattern [28] . Motivation & learning I: the adaptive function of pain, fear & anxiety – avoidance in the face of danger is easy to comprehend, but persistence in this situation is not easy to understand Emotions, such as fear and anxiety, may serve as the coordinates of physiological, cognitive, motivational, and behavioral responses in patterns that increase one’s ability to meet the adaptive challenges of situations [47] . In comparison, pain serves as a signal of the actual or possible threat of body damage in order to motivate protective behaviors [30] . Research on pain and emotional processing has a long tradition of exploring the role of the mechanisms of associative learning in the generalization of pain and fear to situations that are not innately
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Fear & anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance causal. Due to the processes of classical conditioning, a behavioral response to pain will be elicited over time by numerous external and internal stimuli [19] that occurred shortly before the original stimulus occurred. In the case of real harm, this situation may be adaptive, which Nesse and Ellsworth noted by stating that ‘fear two seconds before a danger is far better than two seconds after’ [47 p.132], in stimulating protective behaviors. Situational cues, such as discriminative stimuli, inform the individual about the possible outcomes of a specific behavior, including whether escape will lead to pain reduction, or whether a situation, in general, allows escape/avoidance [48] . Persistence in an activity despite experiencing severe pain, fear or anxiety represents a fight response that is a substantial part of the flight/fight/freezing system [40] . Research in animals is mostly concerned with the effects of the flight or freezing responses. When using mice and cats, this may be plausible because flight would be the most adaptive strategy when escape is possible, while freezing would occur when there is no way to escape. Fighting would lead to death in animals. In humans, most pain situations allow certain types of fighting such as the maintenance of a certain activity despite experiencing pain. There is ample evidence that persistence behavior, despite the presence of elevated pain, is reported to occur equally as or even more often than avoidance in patients who suffer from back pain [20,49–51] . When & why do we fight in the face of danger? Fight or flight responses (escape or persistence) when pain and fear signal threat, imply that making a decision between these responses is possible. Research on motivation and goaldirected behavior has introduced this perspective in pain research [52–55] . Individual goal conflicts besides pain severity have an impact on pain anxiety, which in turn, mediates the effects of pain on disability [53] . In daily life, pain normally interrupts ongoing activities [54] , which requires activation of goal-directed behavior and enables an individual to realize that there is a context-sensitive balance between these antagonistic challenges [56] . Effective goal shielding increases task persistence, which is mediated by certain moderator variables, such as individuals’ level of commitment to a goal, their goal-related tenacity and
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the degree of anxiety and depression [57] . In an elegant experiment, Crombez and colleagues [58] demonstrated that healthy volunteers reported higher effort in order to persist in a cognitive task when they were confronted with a pain stimulus. Moreover, Rachman [59] argued in an interesting monograph, that people persist in threatening activities despite fear, when a specific motivation or commitment, drives these activities. How do we respond to danger? The role of emotion regulation Emotion regulation, by which humans modify the onset or the outcomes of emotions, encompasses a broad set of conscious and non-volitional cognitive, physiological and behavioral responses [60] . Cognitive processing, including attention direction toward or away from a threatening stimulus and the appraisal of a situation play a significant role in one’s resulting emotional state. Research in attention direction has a long tradition in using experimental pain research [61,62] . Focused distraction as a strategy to direct attention away from a threatening pain stimulus to a distracting stimulus has been shown to reduce pain sensitivity and increase pain tolerance [61,62] . However, similar effects have been shown in regard to monitoring the sensory sensations of pain [63] . In contrast, different types of unfocused distraction, where people are instructed to suppress their thoughts about pain or unwanted thoughts, yielded less conclusive results. Thought suppression also led to attention diversion but revealed a high percentage of failures [64] . Interestingly, most people prefer distraction from pain to pain monitoring [62] , and, even in regard to chronic pain thought suppression appeared to be reported most often [14,28,49] . Modern appraisal theories specify certain characteristics of situations that matter for survival, well-being and success in attaining goals [47,65,66] . An individual’s appraisal of situations that produce novelty, unpredictability, or goal obstacles plays a significant role in emotion processing including one’s awareness of emotions and their regulation. In the context of pain, fear and anxiety, there is substantial evidence that reappraisal and acceptance of feelings of distress represent adaptive forms of cognitive emotion regulation [41,67–69] . In contrast, interpreting a pain stimulus to be highly threatening appears
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Review Hasenbring, Chehadi, Titze & Kreddig to be dysfunctional when there is no real threat or when the threat of pain is overinterpreted [70] . However, there is no doubt that appraisal of real danger as threatening may increase the efficacy of the warning signal function. Motivation & learning II: when pain, fear & anxiety turn into maladaptivity Due to their functions as signals that indicate possible threat, pain, fear and anxiety should continue to be seen as transient states of arousal. Maladaptivity in regard to these responses may occur in the following three conditions: first, when these states are elicited in situations where no real threat is present (generalization over situations); second, when the time needed for the solution of the problem, such as healing time, is excessive (maintenance over time); third, when intensity exceeds (situational amplification) or falls below a certain level where coordinated action is not possible. The impairment or loss of the warning function leads to detrimental effects such as a delay in wound healing [71] or a reduction in life expectancy in patients with congenital insensitivity to pain [72] . Generalization over situations and maintenance over time, when no real threat of physical damage is detectable, can be explained by using a combination of the theories of learning, motivation, and emotion processing. Due to substantial work by Fordyce [48] , who explored the role of associative learning in the maintenance of fear and pain, we know that avoidance behavior often becomes a stable response, even when real physical danger is not present. Avoidance may be negatively reinforced when it effectively reduces the fear of pain or of pain-irrelevant distress (see for illustration Box 1, Part 3). In terms of goal pursuit theory, Sam was in a situation of goal facilitation, where one goal (e.g. to avoid of stress at work) effectively was pursued by another goal (avoidance of pain due to long truck drives) [73] . In terms of learning theory, avoidance behavior becomes functional in regard to other goals besides pain [10,11,48] . Furthermore, predispositional factors, such as high levels of anxiety sensitivity or environmental stress, are shown to increase one’s likelihood of developing conditioned responses to fear and associated avoidance [16,38,74] . In contrast to avoidance, persistence despite pain becomes maladaptive if the pain signals real physical harm. Causing physical damage when persisting in repetitive or ongoing activities
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may be likely in regard to activity-dependent pain [30,31] , where the processes of healing after acute damage should be allowed to occur. As described above, uncertainty exists in regard to the presence of real physical danger, which causes a certain degree of anxiety. Preliminary narrative [15] and systematic reviews [75] revealed positive cross-sectional associations between pain persistence and the intensity of back pain. As reported above, persistence and anxiety was shown in a specific subgroup of patients with subacute low back pain, who displayed a DER pattern [14] . In several prospective studies, DER patients have been shown to have maladaptive strategies in terms of pain and disability in the long term [14,28,76] . By measuring accelerometer-based physical activity, research found that these patients demonstrated the highest levels of specific strain postures despite experiencing pain [20,21] , which presumably led to a suboptimal pattern of motor control and real physical damage [4] . In the short term, persistence despite pain is suggested to be maintained by the mechanisms of operant learning. Persistence in a pain-irrelevant task despite the experience of pain may lead to an increase in pain tolerance, which facilitates the pursuit of pain-irrelevant goals [77–80] . The reduction of pain, the increase of tolerance and the successful pursuit of painirrelevant goals serve as reinforcing stimuli that are known to stabilize relevant behavior. In the long term, persistence despite severe pain, may lead to ongoing or repetitive overuse/overload of physical structures, such as muscles or discs, which may lead to and maintain chronic states of pain and disability (see the illustration in Box 1, Part 4) [3,4,20,21,33] . Amplification of pain, fear and anxiety involves conscious and non-volitional interpretations of a pain stimulus as highly threatening (catastrophizing) and attention direction towards the threatening aspects of pain (hypervigilance) [81,82] . The tendency to evaluate a pain stimulus, which is caused for example, by a slight transient biomechanical load, as highly threatening (‘Do I have a fracture?’), may initiate a circuit of feedback mechanisms, that elicit fear and increased physiological arousal, which, in turn, serves as a stimulus that intensifies the threatening appraisal (‘There must be a fracture! It would be a catastrophe if I had to interrupt my work!’) [83,84] . In the fear-avoidance pathway, individuals are suggested to volitionally check the surroundings in order to effectively avoid future threats.
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Fear & anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance A more non-volitional mode of hypervigilance was suggested as part of a paradoxical response to the cognitive suppression of pain, fear or anxiety (‘Do not think about your pain!’). There is substantial evidence from experimental research that these attempts to remove unwanted thoughts from awareness often fail. Moreover, a rebound phenomenon was observed that led to a nonvolitional increase in attention direction towards unwanted feelings and thoughts [85,86] that may lead to the maintenance of anxiety or pain. This increased attention to unwanted thoughts may reflect a non-volitional, automatic type of attention direction, that appears as ‘amplification’ or ‘non-volitional hypervigilance’ [85,86] . A recent meta-analysis on emotion regulation in affective disorders provided substantial evidence for the positive associations between thought suppression and anxiety disorders [67] . In regard to pain, experimental research indicated paradoxical increases of pain and distress that were caused by the instruction to suppress thoughts about pain during a painful stimulation [77–79] . In sum, processes of emotion regulation and goal pursuit that are automatic or more deliberate, work in concert with processes of associative learning that lead to maladaptive forms of pain, fear, and anxiety. This maladaptivity occurs when pain is generalized over many situations that are not innately threatening, in the case of maintenance over normal healing time and in the case of dysfunctional amplification. Especially in the phase of subacute pain, one of the most crucial challenges is to determine whether a pain stimulus signals real or potential physical damage or not and to decide, how to evaluate the severity of this damage and handle high levels of uncertainty. Conclusion & future perspective There is substantial evidence that fear and anxiety, common responses to pain in daily life, play a significant role in the transition between acute and chronic pain. While extensive research has References Papers of special note have been highlighted as: • of interest 1
2
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supported the concepts of a fear–avoidance pathway, recent findings support the existence of additional pathways that include elevated endurance coping as an important mediator in the development of chronic pain and disability. Most evidence is reported in the field of nonspecific low back pain, although pain persistence has already been described in regard to different pain disorders, such as fibromyalgia [87] or sciatic pain [28,76,88] . These findings demonstrate that there is no causal link between pain-related fear/ anxiety and avoidance behavior. Instead, under some circumstances, endurance coping may be an alternative response to pain or fear/anxiety. Over the next 5 to 10 years, the integration of the mechanisms of associative learning, motivation and emotion regulation will help researchers to understand the questions of how and why individuals might respond with rigid and extensive avoidance or endurance that increases the risk of long-term suffering. The AEM provides extensions of the fear–avoidance pathway that elucidate pain responses such as thought suppression and task persistence despite the experience of severe pain and even despite experiencing fear and anxiety. These concepts deliver evidence that is based on the rationale regarding individually targeted strategies of pain management that include more effective patient reassurance [89] and cognitive-behavioral treatments [90] . Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Writing assistance was utilized in the production of this manuscript. The manuscript was edited by American Journal Experts with the costs covered by the authors’ department (Department of Medical Psychology & Medical Sociology, Ruhr-University of Bochum). existing theories. Changes at multiple levels of the nervous system are reviewed introducing the distinction between short term benefits (e.g., protection of the injured and painful part) and long term consequences (e.g., an increase of load and decrease of movement).
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