The Concept of Contexts in Pain: Generalization of Contextual Pain-Related Fear Within a de Novo Category of Unique Contexts

The experience of unpredictable pain fluctuations can trigger anticipatory pain-related fear. When discrete predictors for pain are lacking, fear typically accrues to the broader environmental context: a phenomenon referred to as contextual pain-related fear. We examined whether conceptual similarity between discrete contexts facilitates pain-related fear generalization; this mechanism is known as category-level fear generalization. Using a voluntary joystick movement paradigm, pain-free participants performed movements in 2 contexts (within-subjects design); context was manipulated by varying background color screens. In the predictable context, one movement predicted pain and another did not. In the unpredictable context, 2 other movements never predicted pain but pain was unpredictably delivered during the context. Participants subsequently learned to categorize novel background colors (ie, generalization contexts) as being similar to either the unpredictable or predictable pain context. Then we tested fear generalization to these novel contexts. We measured self-reported pain-related fear, expectancy, and eyeblink startle. Results indicated higher pain-related fear reports, but no elevated startle responses, for generalization contexts that were trained to be similar to the original unpredictable context rather than the predictable pain context. This highlights a potential pathway through which neutral contexts can elicit pain-related fear and motivate avoidance behavior associated with chronic pain disability.

Reduction of fear of movement-related pain and pain-related anxiety: An associative learning approach using a voluntary movement paradigm

The fear-avoidance model advances fear of pain as a key factor in the origins of chronic pain disability. Initial evidence in those with chronic back pain reveals that exposure therapy reduces fear levels, disability, and pain. Despite the success of exposure in the clinic, fundamental research about its underlying mechanisms lags behind. Using a conditioning paradigm with movements as conditioned stimuli (CS) and a painful shock as unconditioned stimuli (US), we investigated the extinction of experimental fear of movement-related pain and pain-related anxiety (respectively induced by predictable and unpredictable pain). Dependent measures were self-reported fear and eyeblink startle. During acquisition, all groups received both predictable and unpredictable training. In the predictable context, one movement (CS+) was consistently followed by the shock-US, but another movement was not (CS-). In the unpredictable context, joystick movements never signaled the shock-US; shock-US were delivered during the intertrial interval (ITI). During extinction, the extinction group continued training in the predictable context but the CS+ movement was no longer reinforced; the context exposure group continued training in the unpredictable context but ITI shock-US were omitted. The control group continued training after the acquisition reinforcement scheme. Results revealed that fear ratings for the CS+ were extinguished in the extinction group but not in the control group. Interestingly, omitting the ITI shocks not only reduced ITI startle responses in the context exposure group compared with the control group, but also reduced the fear ratings and startle responses elicited by the unpredictable CS. The clinical implications of these findings are discussed.     

The acquisition and generalization of cued and contextual pain-related fear: An experimental study using a voluntary movement paradigm

Recent evidence indicates that pain-related fear can be acquired through associative learning. In the clinic, however, spreading of fear and avoidance is observed beyond movements/activities that were associated with pain during the original pain episode. One mechanism accounting for this spreading of fear is stimulus generalization. In a voluntary movement-conditioning paradigm, healthy participants received predictable pain (ie, one movement predicts pain, another does not) in one context, and unpredictable pain in another context. The former procedure is known to induce cued pain-related fear to the painful movement, whereas the latter procedure generates contextual pain-related fear. In both experimental pain contexts, we subsequently tested fear generalization to novel movements (having either proprioceptive features in common with the original painful movement or nonpainful movement). Results indicated that in the predictable pain context, pain-related fear spreads selectively to novel movements proprioceptively related to the original painful movement, and not to those resembling the original nonpainful movement. In the unpredictable context, nondifferential fear generalization was observed, suggesting persistent contextual pain-related fear and poor safety learning. These data illustrate that spreading of pain-related fear is fostered by previously acquired movement-pain contingencies. Based on recent advances in anxiety research, we proposed an innovative approach conceptualizing predictable pain as a laboratory model for fear of movement in regional musculoskeletal pain, and unpredictable pain generating contextual pain-related fear as a prototype of widespread musculoskeletal pain. Consequently, fear generalization might play an important role in spreading of pain-related fear and avoidance behavior in regional and widespread musculoskeletal pain.     

Mere Intention to Perform Painful Movements Elicits Fear of Movement-Related Pain: An Experimental Study on Fear Acquisition Beyond Actual Movements

Fresh empirical evidence supports the notion that fear of movement-related pain can be acquired through associative learning. In the context of these findings, 2 ideas are appealing, yet uninvestigated. The first is that merely the intention to perform a painful movement acts as a covert conditioned stimulus (CS) inducing defensive fear responses (ie, gaining excitatory properties following Pavlovian acquisition). The second idea is that after extinction, fear of movement-related pain can easily be reinstated after unexpected painful stimuli (ie, reinstatement). In a voluntary differential conditioning movement paradigm with movements as CSs and a painful electrocutaneous stimulus as the unconditioned stimulus (pain-US), 2 groups were included (Experimental/Control). One movement (CS+) was followed by the pain-US and another movement (CS?) was not during acquisition, while the CS+ was no longer reinforced during extinction. Next, the Experimental group received 2 reinstating pain-USs, whereas the Control group did not. The CS+ but not the CS? evoked fear of movement-related pain in self-reports and eye-blink startles. Intriguingly, the mere intention to perform the painful movement produced higher eye-blink startle responses than the intention to perform the nonpainful movement. We also demonstrated nondifferential reinstatement in the verbal fear ratings in the Experimental group only.PerspectiveThis study demonstrates that the mere intention to perform a painful movement prior to the actual painful movement itself can come to elicit conditioned fear responses. These results suggest that actual movement may not be necessary to elicit pain-related fear responses, maintaining chronic pain-related fear, avoidance, and disability.     

The acquisition of fear of movement-related pain and associative learning: a novel pain-relevant human fear conditioning paradigm

Current fear-avoidance models consider fear of pain as a key factor in the development of chronic musculoskeletal pain. Generally, the idea is that by virtue of the formation of associations or acquired propositional knowledge about the relation between neutral movements and pain, these movements may signal pain, and hence start to elicit defensive fear responses (eg, avoidance behavior). This assumption has never been investigated experimentally. Therefore, we developed a pain-relevant fear conditioning paradigm using a movement as a conditioned stimulus (CS) and a painful electrocutaneous stimulus as an unconditioned stimulus (US) to examine the acquisition of fear of movement-related pain in healthy subjects. In a within-subjects design, participants manipulated a joystick to the left/right in the experimental (predictable) condition, and upward/downward in the control (unpredictable) condition or vice versa. In the predictable condition, one movement direction (CS+), and not the other (CS−), was followed by painful stimuli. In the unpredictable condition, painful stimuli were always delivered during the intertrial interval. Both fear of movement-related pain ratings and eyeblink startle measures were more elevated in response to the CS+ than to the CS−, whereas no differences occurred between both unreinforced CSs in the control condition. Participants were slower initiating a CS+ movement than a CS− movement, while response latencies to CSs in the control condition did not differ. These data support the acquisition of fear of movement-related pain by associative learning. Results are discussed in the broader context of the acquisition of pain-related fear in patients with musculoskeletal pain.     

Verbal Instruction Can Induce Extinction of Fear of Movement-Related Pain

The fear avoidance model of chronic musculoskeletal pain highlights the importance of pain-related fear in chronification of pain. Although several interventions have been developed on the basis of this model, the following issues remain unresolved: first, whether movement conditioned to pain can evoke fear responses particularly sympathetic activation, and second, whether verbal instructions can attenuate conditioned fear of movement-related pain as with direct experience. To investigate these issues, we induced proprioceptive conditioning (learning the relationship between proprioceptive sensations and an aversive event) and extinction learning in healthy volunteers, and we compared psychophysiological and subjective indices of fear between an instructed and a normal extinction group. Using paired presentation of painful heat stimuli as an unconditioned stimulus and flexion of the wrist as a conditioned stimulus, all participants acquired the conditioned fear response (skin potential response) to the conditioned stimulus. The instructed extinction group was then told that the movement was no longer followed by painful stimulus at the beginning of the extinction phase, and only this group showed significant decreases on both indices of fear. This finding indicates that verbal instruction can attenuate conditioned fear of movement-related pain, supporting the clinical importance of providing information regarding the relationship between movement and pain.

Generalization and Extinction of Concept-BasedPain-Related Fear

In chronic pain, pain-related fear seems to overgeneralize to safe stimuli, thus contributing to excessive fear and avoidance behavior. Evidence shows that pain-related fear can be acquired and generalized based on conceptual knowledge. Using a fear conditioning paradigm, we investigated whether this concept-based pain-related fear could also be extinguished. During acquisition, exemplars of 1 action category (conditioned stimuli [CSs]; eg, opening boxes) were followed by pain (CS+), whereas exemplars of another action category were not (CS–; eg, closing boxes). Participants reported more pain-related fear and expectancy toward exemplars of the CS+ category compared with those of the CS– category. During generalization, fear and expectancy spread to novel exemplars (generalization stimuli [GSs]) of the CS+ category (GS+), but not to those of the CS– category (GS–). During extinction, exemplars of both categories were presented in the absence of pain. At the end of extinction, participants no longer reported elevated fear or expectancy toward CS+ exemplars compared to CS– exemplars. These findings were not replicated in either the eye-blink startle or skin conductance measures. This is the first study to demonstrate extinction of concept-based pain-related fear, thus providing evidence for the potential of extinction-based techniques in the treatment of conceptual pain-related fear.

Positive Affect Protects Against Deficient Safety Learning During Extinction of Fear of Movement-Related Pain in Healthy Individuals Scoring Relatively High on Trait Anxiety

From a treatment perspective, it is highly relevant to pinpoint individual vulnerability factors for resistance to exposure treatment in highly fearful chronic pain patients. Previous fear conditioning research showed that healthy individuals scoring relatively high on trait anxiety display sustained fear to safety cues during extinction. In the context of fear of movement-related pain, this intriguing question has been largely neglected so far. Even more importantly, positive psychological traits such as trait positive affect may function as protective factors against the spreading of fear to safe movements and improve exposure treatment outcomes. In this study, healthy participants completed a trait anxiety and trait positive affect questionnaire and underwent acquisition and extinction of fear of movement-related pain using an experimental voluntary movement paradigm. During acquisition, one movement (CS+) was paired with a painful stimulus and another movement was not (CS?). During extinction, the CS+ was no longer reinforced. Results show failure of fear inhibition to the CS? during extinction in healthy individuals scoring relatively high on trait anxiety or relatively low on positive affect. These findings seem to suggest that safety learning is more vulnerable in healthy people with a high anxious disposition and/or relatively lower levels of positive affect. In addition, this is the first study to show that the negative impact of high trait anxiety on fear inhibition to safety cues during extinction can be countered by high levels of positive affect. These findings may have important clinical implications.PerspectiveBoth low positive affect and high trait anxiety are associated with impaired fear inhibition to nonpainful movements during fear extinction. Interestingly, high levels of positive affect buffer against the negative impact of trait anxiety. Increasing positive affect during exposure may counter the effects of trait vulnerabilities and improve treatment outcomes.     

Observational Learning and Pain-Related Fear: An Experimental Study With Colored Cold Pressor Tasks

The primary aim of the current study was to experimentally test whether pain-related fear can be acquired through observational learning, whether extinction occurs after actual exposure to the aversive stimulus, and whether pain-related fear was associated with increased pain ratings. During an observation phase, female volunteers watched a video showing models performing cold pressor tasks (CPT), of which the color served as a conditioned stimulus (CS). In a differential fear conditioning paradigm, each of 2 colors were either paired with models’ painful (CS+) or neutral (CS−) facial expressions. Exposure consisted of participants performing CPTs of both colors (10°C). Self-reported fear of pain and expected pain ratings were obtained after the observation period, while actual pain and avoidance measures were obtained during and after exposure. Results show that after observing another person performing the CPT associated with the painful faces, subjects report more fear of pain and expect more intense and unpleasant pain as compared with the CPT associated with the neutral faces. This effect of observational learning on pain-related fear persisted until after exposure. During and after exposure no stimulus-type effect for pain ratings was found. This study provides preliminary evidence for observational learning of pain-related fear in humans.

Perspective

Fear of pain can be more disabling than pain itself, and is a risk factor for chronic pain. Knowledge about the acquisition of pain-related fear may help to develop novel pain management programs. This study is one of the first to demonstrate the effects of observational learning on pain-related fear.     

Extinction of Fear Generalization: A Comparison Between Fibromyalgia Patients and Healthy Control Participants

Fear learning deficiencies might contribute to the development and maintenance of chronic pain disability. Fear is often not restricted to movements (conditioned stimulus [CS+]) originally associated with pain (unconditioned stimulus), but expands to similar movements (generalization stimuli [GSs]). This spreading of fear becomes dysfunctional when overgeneralization to safe stimuli occurs. More importantly, persistence of pain-related fear to GSs despite corrective feedback might even be more debilitating and maintain long-term chronic pain disability. Yet, research on this topic is lacking. Using a voluntary joystick movement paradigm, we examined (extinction of) pain-related fear generalization in fibromyalgia patients (FM) and healthy control participants (HC). During acquisition, one movement (CS+) predicted pain; another did not (CS?). We tested (extinction of) fear generalization to 5 GSs varying in similarity with the CS+ and CS?. Results revealed flatter pain expectancy generalization gradients in FM than in HC due to elevated responses to GSs more similar to the CS?; the fear generalization gradients did not differ. Although pain-related fear and expectancy to the GSs decreased during extinction, responses to the GSs remained higher for FM than HC, suggesting that extinction of generalization is impaired in chronic pain patients. Persistence of excessive protective responses may contribute to maintaining long-term chronic pain disability.

Biased Intensity Judgements of Visceral Sensations After Learning to Fear Visceral Stimuli: A Drift Diffusion Approach

A growing body of research has identified fear of visceral sensations as a potential mechanism in the development and maintenance of visceral pain disorders. However, the extent to which such learned fear affects visceroception remains unclear. To address this question, we used a differential fear conditioning paradigm with nonpainful esophageal balloon distensions of 2 different intensities as conditioning stimuli (CSs). The experiment comprised of preacquisition, acquisition, and postacquisition phases during which participants categorized the CSs with respect to their intensity. The CS+ was always followed by a painful electrical stimulus (unconditioned stimulus) during the acquisition phase and in 60% of the trials during postacquisition. The second stimulus (CS?) was never associated with pain. Analyses of galvanic skin and startle eyeblink responses as physiological markers of successful conditioning showed increased fear responses to the CS+ compared with the CS?, but only in the group with the low-intensity stimulus as CS+. Computational modeling of response times and response accuracies revealed that differential fear learning affected perceptual decision-making about the intensities of visceral sensations such that sensations were more likely to be categorized as more intense. These results suggest that associative learning might indeed contribute to visceral hypersensitivity in functional gastrointestinal disorders.

The Opportunity to Avoid Pain May Paradoxically Increase Fear

Fear-avoidance models propose that pain-related fear may spur avoidance behavior leading to chronic pain disability. Pain-related fear elicits avoidance behavior, which is typically aimed at reducing fear. We hypothesized that engaging in avoidance may (paradoxically) increase rather than decrease pain-related fear (ie, bidirectionality hypothesis). In a between-subject design, participants (n?=?64) were randomly assigned to the avoidance group or the control group. Avoidance group participants were led to believe they could avoid full exposure to a painful heat stimulus by pressing the stop button, whereas control group participants believed they were exposed to the full painful heat stimulus at all times. In reality and unknown to the participants, the intensity and duration of the heat stimulus was independent of the avoidance response, and was identical in both groups. During the test, the avoidance response (ie, pressing the stop button) was no longer available. As expected, pain-related fear levels were higher after avoiding the painful heat stimulus. Interestingly, in the avoidance group, pain-related fear increased after receiving instructions that avoidance would be possible, even before actually engaging in avoidance behavior. In the control group, no significant change was observed in pain-related fear throughout the experiment. The eyeblink startle measures did not corroborate this data pattern.

Women, but not men, report increasingly more pain during repeated (un)predictable painful electrocutaneous stimulation: Evidence for mediation by fear of pain

An abundance of animal research suggests that fear inhibits pain whereas anxiety increases it. Human studies on this topic are more scarce, and the existing evidence seems rather inconsistent. Therefore, we aimed to investigate the divergent effects of both negative emotional states-that is, pain-related fear and anxiety on pain sensitivity and unpleasantness. Possible sex-related differences were also under investigation, as well as the potential mediational role of fear of movement-related pain on the differences in pain intensity and unpleasantness between both sexes. We employed a voluntary joystick movement paradigm using movements as conditioned stimuli (CSs) and a painful electrocutaneous stimulus as the unconditioned stimulus. Healthy participants received predictable shocks in one condition and unpredictable shocks in another condition. The former procedure is known to induce fear of movement-related pain to the CS+ movement (movement consistently followed by pain), whereas the latter procedure induces (contextual) pain-related anxiety. Results showed that fear of movement-related pain indeed resulted in decreased pain intensity/unpleasantness ratings, while pain-related anxiety led to increased pain intensity/unpleasantness reports. Further, the anticipated sex difference was modulated by time. That is, women gradually reported more pain/unpleasantness, whereas men do not show such a sensitization effect. Moreover, this sex-specific sensitization is partially mediated by (conditioned) fear of movement-related pain. Women also report increasingly more fear of pain over conditioning blocks, while men do not. These results might be interesting in the light of the overrepresentation of women in a number of clinical pain conditions as well as anxiety disorders.     

Observational Learning and Pain-Related Fear: Exploring Contingency Learning in an Experimental Study Using Colored Warm Water Immersions

This study investigated observational learning of pain-related fear and subsequent extinction after first-hand exposure to the feared stimulus. Moreover, the specific contingencies that are learned when observing others in pain were explored. A differential fear-conditioning paradigm was used, showing video models displaying either a painful (CS+ color; aversively conditioned stimulus) or a neutral (CS? color; neutrally conditioned stimulus) facial expression in the presence of a colored warm water task (WWT; observation phase). In 1 condition (open WWT cover), the model's hand was immersed in the colored liquid, while in the other condition (closed WWT cover), no contact was displayed between the model and the liquid. During exposure, participants subsequently immersed their own hand into each WWT with equal temperatures. Results revealed successful acquisition of pain-related fear. Participants with higher levels of pain catastrophizing, intolerance of uncertainty, trait fear of pain, or dispositional empathy were more prone to develop pain-related fear. Pain-related fear extinguished quickly after direct exposure to both WWTs. Contingencies between the color of the WWT and either the painful facial expressions or the assumed properties of the colored liquid were learned in both conditions. Clinical implications and limitations of the current study are discussed, providing avenues for future research in observational learning of pain-related fear.PerspectivePain-related fear promotes the development as well as the continuation of chronic pain. A better understanding of the acquisition and extinction of this fear may help to improve pain treatment programs. Furthermore, we intended to identify individuals who are more prone to develop pain-related fear.     

Fear of pain and defensive activation

Fear of pain and its relationship to dental fear was investigated by measuring autonomic reactions (skin conductance and heart rate) in individuals reporting high and low dental fear when in the presence of a cue that threatened the presentation of electric shock ("threat") or not ("safe"). Acoustic startle probes were also presented during both threat and safe periods, and the reflexive eye blink, the skin conductance response, and cardiac changes to the startle probe measured. All participants reacted with greater defensive reactivity, including potentiated startle blinks, heightened skin conductance, and cardiac deceleration in the context of threat, compared to safe, cues. Individuals reporting high dental fear were significantly more reactive during threat periods, compared to low fear individuals, showing larger blink reflexes and heightened electrodermal activity, as well as heightened autonomic responses to the startle probe itself. Individual differences in defensive reactivity persisted even after participants received a single mild shock halfway through the experiment. The data indicate that threat of shock elicits heightened defensive reactivity in those reporting high dental fear, consistent with the hypothesis that fear of potentially painful events may be a potent mediator of the anxiety involved in anticipated medical and dental treatment.     

The role of learning in nocebo and placebo effects

The nocebo effect consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Here we show that nocebo suggestions, in which expectation of pain increase is induced, are capable of producing both hyperalgesic and allodynic responses. By extending previous findings on the placebo effect, we investigated the role of learning in the nocebo effect by means of a conditioning procedure. To do this, verbal suggestions of pain increase were given to healthy volunteers before administration of either tactile or low-intensity painful electrical stimuli. This nocebo procedure was also carried out after a pre-conditioning session in which two different conditioned visual stimuli were associated to either pain or no-pain. Pain perception was assessed by means of a Numerical Rating Scale raging from 0 = tactile to 10 = maximum imaginable pain. We found that verbal suggestions alone, without prior conditioning, turned tactile stimuli into pain as well as low-intensity painful stimuli into high-intensity pain. A conditioning procedure produced similar effects, without significant differences. Therefore, in contrast to placebo analgesia, whereby a conditioning procedure elicits larger effects compared to verbal suggestions alone, learning seems to be less important in nocebo hyperalgesia. Overall, these findings indicate that, by defining hyperalgesia as an increase in pain sensitivity and allodynia as the perception of pain in response to innocuous stimulation, nocebos can indeed produce both hyperalgesic and allodynic effects. These results also suggest that learning is not important in nocebo hyperalgesia compared to placebo analgesia.     

Illusion of pain: pre-existing knowledge determines brain activation of 'imagined allodynia'.

Allodynia means that innocuous tactile stimulation is felt as pain. Accordingly, cerebral activations during allodynia or touch should markedly differ. The aim of this study was to investigate whether the imagination of allodynia affects brain processing of touch in healthy subjects. Seventeen healthy subjects divided into 2 subgroups were investigated: The first group (n = 7) was familiar with allodynia, based on previous pain studies, whereas the second group (n = 10) had never knowingly experienced allodynia. Using functional magnetic resonance imaging, 2 experimental conditions were investigated. In one condition the subjects were simply touched at their left hand, whereas during the other condition they were asked to imagine pain (allodynia) during tactile stimulation of the right hand and to estimate the imagined pain on a numeric rating scale. Data processing and analysis were performed with the use of SPM5. The group analysis of all subjects revealed that tactile stimulation activated contralateral somatosensory cortices (S1 [primary] and S2 [secondary]), but the imagination of allodynia led to an additional activation of anterior cingulate cortex and bilateral activation of S2, insular cortex, and prefrontal cortices. Subgroup analysis using rating-weighted predictors revealed activation of the contralateral thalamus, anterior cingulate cortex, and amygdala and a bilateral activation of S1, S2, and insular cortex and prefrontal cortices in allodynia-experienced subjects. In contrast, allodynia-inexperienced subjects only activated contralateral S1 and bilateral S2. Just the imagination that touch is painful is able to partly activate the central pain system, but only when the subject has previous experience of this. According to our results, the medial pain system is involved in the encoding of imagined allodynia. PERSPECTIVE: This article reports that pain experience is able to alter central processing of sensory stimuli. Pain knowledge appears to be able to shift "normal" tactile processing to a different quality, resulting in modified brain activity. Therefore, our study may contribute to the current understanding of human pain and will promote future research on this field.     

Heterotopic noxious conditioning stimulation (HNCS) reduced the intensity of spontaneous pain, but not of allodynia in painful peripheral neuropathy.

In 15 patients with painful peripheral neuropathy and dynamic mechanical allodynia, the influence of spontaneous ongoing neuropathic pain on pain sensitivity in a remote pain-free area was examined, as was the influence of ischemia-induced heterotopic noxious conditioning stimulation (HNCS) on the intensity of ongoing pain and brush-evoked allodynia. In addition, the modulating effect of HNCS on pain sensitivity in a pain-free area was investigated. Pain thresholds to pressure and heat as well as the sensitivity to suprathreshold pressure- and heat pain were assessed in the pain-free area. Dynamic mechanical allodynia was induced by a recently developed semi-quantitative brushing technique and the patients continuously rated the intensity of the allodynia using a computerized visual analogue scale (VAS). The total brush-evoked pain intensity was calculated as the area under the VAS curve. At baseline, no significant difference in pain sensitivity was found between patients and their healthy controls in the pain-free area, indicating a lack of activation of pain modulatory systems from the spontaneous pain. Compared to baseline, the patients rated the ongoing neuropathic pain intensity significantly lower during the HNCS-procedure (p<0.05). In contrast, there was no influence from HNCS on the total brush-evoked pain intensity. In the pain-free area higher pressure pain thresholds were demonstrated during conditioning stimulation in patients and controls alike (p<0.01). In controls only, a significantly higher heat pain threshold was found during the HNCS-procedure (p<0.01). The main finding of the present study was that HNCS altered differentially spontaneous and brush-provoked pain in patients with painful peripheral neuropathy.     

Once an Avoider Always an Avoider? Return of Pain-Related Avoidance After Extinction With Response Prevention

In exposure for chronic pain, avoidance is often forbidden (extinction with response prevention; RPE) to prevent misattributions of safety. Although exposure is an effective treatment, relapse is common. Little is known about the underlying mechanisms of return of pain-related avoidance. We hypothesized that pain-related avoidance would recover when becoming available again after RPE and after unexpected pain episodes (“reinstatement”), especially when restricting avoidance during RPE (compared to instructing not to use it). In an operant pain-related avoidance conditioning paradigm, healthy volunteers used a robotic arm to perform various arm reaching movements differing in pain-effort trade-off. During acquisition, participants learned to avoid pain by performing more effortful movements. During RPE they only performed the formerly pain-associated movement under extinction, and were either forbidden (Restricted group) or merely instructed (Instructed group) not to perform other movements. One day later, we tested spontaneous recovery and reinstatement of pain-related fear and avoidance with availability of all movements. Results showed that pain-related fear and avoidance re-emerge after RPE, though not to pretreatment levels. The reinstatement manipulation had no additional effect. No group differences were observed. We discuss findings in the context of learning processes in (chronic) pain disability and relapse prevention in chronic pain treatment.Perspective: Using experimental models of relapse, we investigated the return of pain-related avoidance behavior after extinction with response prevention. Findings are potentially informative for clinicians performing exposure treatment with chronic pain patients.     

The Influence of Conditioned Fear on Human Pain Thresholds: Does Preparedness Play a Role?

Emotionally charged facial expressions (happy, fear) served as conditioned stimuli in a differential fear conditioning procedure. Expressions were presented in pseudo-random order on a computer monitor. For half of the participants, the fear expression was paired with an aversive electric stimulation (UCS), whereas the happy expression was unpaired. The other participants had the opposite pairing. To assess the influence of conditioned fear on pain, expressions were shown again in the absence of the UCS and pain threshold was assessed during each expression. The latency of finger withdrawal from a radiant heat device was used to index pain threshold. Skin conductance response (SCR) and self-reported emotion were measured to assess fear conditioning. Consistent with preparedness theory, differential fear conditioning was only present when the fear expression was paired with the UCS. Moreover, pain threshold was only influenced by fear conditioning in persons for whom the fear expression was paired with the UCS. Specifically, finger withdrawal latencies were lower (suggesting hyperalgesia) during the fear expression than during the happy expression; an effect that was not present before CS-UCS pairing. This work suggests that some stimuli are more readily associated with an aversive event and can lead to pain enhancement. PERSPECTIVE: Although preliminary, these results suggest that fear-relevant environmental stimuli (including facial expressions) may provide important environmental cues during aversive events that influence the level of pain experienced.