Ann Meulders

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

Summary A novel pain‐relevant fear conditioning paradigm that demonstrates the involvement of associative learning in the acquisition of fear of movement‐related pain. ABSTRACT 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.

Don’t fear ‘fear conditioning’: Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear

HighlightsOriginates from discussions on replicability and researchers degrees of freedom.Aims at stimulating discussions on methods applied in fear conditioning research.Addresses critical issues on terminology, design, methods, analysis.Serves as comprehensive compendium and critical evaluation of read‐out measures.Highlights methodological considerations when studying individual differences. ABSTRACT The so‐called ‘replicability crisis’ has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence‐based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning.

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

TOC summary Conditioned fear of movement induced by predictable pain selectively spreads to novel proprioceptively similar movements; in an unpredictable pain context, fear generalization is not stimulus‐specific. ABSTRACT 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.

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.

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

Summary Pain‐related fear and anxiety can be reduced by a Pavlovian extinction procedure. Reducing pain‐related anxiety promotes safety (inhibitory) learning about movements never associated with pain. ABSTRACT 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.

Bogus Visual Feedback Alters Onset of Movement-Evoked Pain in People With Neck Pain

Pain is a protective perceptual response shaped by contextual, psychological, and sensory inputs that suggest danger to the body. Sensory cues suggesting that a body part is moving toward a painful position may credibly signal the threat and thereby modulate pain. In this experiment, we used virtual reality to investigate whether manipulating visual proprioceptive cues could alter movement-evoked pain in 24 people with neck pain. We hypothesized that pain would occur at a lesser degree of head rotation when visual feedback overstated true rotation and at a greater degree of rotation when visual feedback understated true rotation. Our hypothesis was clearly supported: When vision overstated the amount of rotation, pain occurred at 7% less rotation than under conditions of accurate visual feedback, and when vision understated rotation, pain occurred at 6% greater rotation than under conditions of accurate visual feedback. We concluded that visual-proprioceptive information modulated the threshold for movement-evoked pain, which suggests that stimuli that become associated with pain can themselves trigger pain.

Differences in pain-related fear acquisition and generalization: an experimental study comparing patients with fibromyalgia and healthy controls.

Abstract Anomalies in fear learning, such as failure to inhibit fear to safe stimuli, lead to sustained anxiety, which in turn may augment pain. In the same vein, stimulus generalization is adaptive as it enables individuals to extrapolate the predictive value of 1 stimulus to similar stimuli. However, when fear spreads in an unbridled way to novel technically safe stimuli, stimulus generalization becomes maladaptive and may lead to dysfunctional avoidance behaviors and culminate in severe pain disability. In a voluntary movement conditioning paradigm, we compared the acquisition and generalization of pain-related fear in patients with fibromyalgia (FM) and healthy controls. During acquisition, participants received predictable pain in 1 context (ie, 1 movement predicts pain, whereas another does not), and unpredictable pain in another (ie, pain never contingent upon movement). Fear generalization to novel movements (resembling the original painful or nonpainful movement) was tested in both contexts. Results indicated that the FM group showed slower differential acquisition of pain-related fear in the predictable context, and more contextual pain-related fear in the unpredictable context. Fear of movement-related pain spreads selectively to novel movements similar to the original painful movement, and not to those resembling the nonpainful movement in the healthy controls, but nondifferential fear generalization was observed in FM. As expected, in the unpredictable context, we also observed nondifferential fear generalization; this effect was more pronounced in FM. Given the status of overgeneralization as a plausible transdiagnostic pathogenic marker, we believe that this research might increase our knowledge about pathogenesis of musculoskeletal widespread pain.

Competing goals attenuate avoidance behavior in the context of pain

UNLABELLED Current fear-avoidance models consider pain-related fear as a crucial factor in the development of chronic pain. However, pain-related fear often occurs in a context of multiple, competing goals. This study investigated whether pain-related fear and avoidance behavior are attenuated when individuals are faced with a pain avoidance goal and another valued but competing goal, operationalized as obtaining a monetary reward. Fifty-five healthy participants moved a joystick toward different targets. In the experimental condition, a movement to one target (conditioned stimulus [CS+]) was followed by a painful unconditioned stimulus (pain-US) and a rewarding unconditioned stimulus (reward-US) on 50% of the trials, whereas the other movement (nonreinforced conditioned stimulus [CS-]) movement was not. In the control condition, the CS+ movement was followed by the pain-US only. Results showed that pain-related fear was elevated in response to the CS+ compared to the CS- movement, but that it was not influenced by the reward-US. Interestingly, participants initiated a CS+ movement slower than a CS- movement in the control condition but not in the experimental condition. Also, in choice trials, participants performed the CS+ movement more frequently in the experimental than in the control condition. These results suggest that the presence of a valued competing goal can attenuate avoidance behavior. PERSPECTIVE The current study provides experimental evidence that both pain and competing goals impact on behavioral decision making and avoidance behavior. These results provide experimental support for treatments of chronic pain that include an individuals pursuit of valuable daily life goals, rather than limiting focus to pain reduction only.

Generalization gradients in cued and contextual pain-related fear: an experimental study in healthy participants

Increasing evidence supports the notion that pain-related fear plays a key role in the transition from acute to chronic pain. Recent experimental data show that associative learning processes are involved in the acquisition of pain-related fear. An intriguing yet underinvestigated question entails how spreading of pain-related fear in chronic pain occurs. In a voluntary movement paradigm in which one arm movement (CS+) was followed by a painful stimulus and another was not (CS−) in the predictable group and painful stimuli were delivered during the intertrial interval (context alone) in the unpredictable group, we tested generalization of fear to six novel generalization movements (GSs) with varying levels of similarity between the original CS+ movement and CS− movement. Healthy participants (N = 58) were randomly assigned to the predictable or unpredictable group. Fear was measured via verbal ratings and eyeblink startle responses. Results indicated that cued pain-related fear spreads selectively to novel movements that are proprioceptively more similar to the CS+ than to those similar to the CS− in the predictable group, but not in the unpredictable group. This is the first study to demonstrate a generalization gradient of cued pain-related fear. However, this effect was only present in the startle eyeblink responses, but not in the verbal ratings. Taken together, this paradigm represents a novel tool to scrutinize the largely understudied phenomenon of the spreading of fear and avoidance in patients with chronic musculoskeletal pain and mapping possible pathological differences in generalization gradients and the spreading of pain in patients as compared with healthy controls.

Safety behavior can hamper the extinction of fear of movement-related pain: an experimental investigation in healthy participants.

Excessive fear of movement-related pain (FMRP), and its associated avoidance behavior, is considered a major risk factor for disability in chronic musculoskeletal pain. The current study aimed to investigate whether engaging in safety behavior, conceptualized as an avoidance response, hampers the extinction of FMRP. In a differential conditioning paradigm, we used joystick movements as conditioned stimuli (CSs) and a painful electrocutaneous stimulus as the unconditioned stimulus (US). In the Safety group, participants received the opportunity to avoid the pain-US by pressing a safety button during the extinction phase, whereas in the Control group, this option was not included. In a subsequent test phase, this safety button was no longer available. In two experiments, results demonstrate successful acquisition and extinction. Retrospective FMRP ratings in both experiments revealed a return of fear of pain in the test phase in the Safety group, but not in the Control group. In Experiment 1, mean eyeblink startle reflex amplitudes partly corroborated the self-report findings on fear of pain. The present results suggest that performing safety behavior during cognitive-behavioral interventions, i.e., exposure, might increase the risk of a return of FMRP.