Beyond nociception

Pain, 2015

Pain is a biologically relevant signal and response to bodily threat, associated with the urge to restore the integrity of the body. Immediate protective responses include increased arousal, selective attention, escape, and facial expressions, followed by recuperative avoidance and safety-seeking behaviors. To facilitate early and effective protection against future bodily threat or injury, learning takes place rapidly. Learning is the observable change in behavior due to events in the internal and external environmental and includes nonassociative (habituation and sensitization) and associative learning (Pavlovian and operant conditioning). Once acquired, these knowledge representations remain stored in memory and may generalize to perceptually or functionally similar events. Moreover, these processes are not just a consequence of pain; they may directly influence pain perception. In contrast to the rapid acquisition of learned responses, their extinction is slow, fragile, context ...

Pain, 2017

Pain spontaneously activates adaptive and dynamic learning processes affecting the anticipation of, and the responses to, future pain. Computational models of associative learning effectively capture the production and ongoing changes in conditioned anticipatory responses (eg, skin conductance response), but the impact of this dynamic process on unconditional pain responses remains poorly understood. Here, we investigated the dynamic modulation of pain and the nociceptive flexion reflex by fear learning in healthy human adult participants undergoing a classical conditioning procedure involving an acquisition, reversal and extinction phase. Conditioned visual stimuli (CS+) coterminated with a noxious transcutaneous stimulation applied to the sural nerve on 50% of trials (unconditioned stimuli). Expected pain probabilities and cue associability were estimated using computational modeling by fitting a hybrid learning model to skin conductance response elicited by the CS+. Multilevel li...

Neuroscience & Biobehavioral Reviews, 2015

Please cite this article as: Zaman, J., Vlaeyen, J.W.S., Van Oudenhove, L., Wiech, K., Van Diest, I.,Associative fear learning and perceptual discrimination: a perceptual pathway in the development of chronic pain, Neuroscience and Biobehavioral Reviews (2015), http://dx.

Pain, 2020

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Pain, 2005

Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain behavior, but it is not clear whether and how this extends to pain perception itself. The fear-avoidance theory suggests that hypersensitivity may be induced by anticipatory pain avoidance learned through negative reinforcement by acute reductions of pain and fear. But the precise mechanism of the assumed 'sensory decalibration' has not been specified. The present study with healthy subjects investigated whether operant learning of enhanced short-term sensitization may provide the 'proximal' mechanism and whether gradual learning of hypersensitivity can take place without subjects' awareness. We used an experimental model of implicit learning based on a behavioral adjustment method of sensitization measurement developed and validated previously, combining it with standard methods of operant response shaping of increased sensitization or habituation. Results indicated that operant discrimination training with reinforcement of short-term sensitization in the seconds range can produce gross up or down changes in sensitivity within an hour without subjects' awareness of reinforcement contingencies. Consequently, implicit learning of enhanced pain sensitization may be a suitable model to investigate operant plasticity of pain perception in addition to basic sensory and neuronal mechanisms and to link these with the clinical construct of pain-fear avoidance. q

Proceedings of the National Academy of Sciences, 2000

Associative learning is thought to depend on detecting mismatches between actual and expected experiences. With functional magnetic resonance imaging (FMRI), we studied brain activity during different types of mismatch in a paradigm where contrastingcolored lights signaled the delivery of painful heat, nonpainful warmth, or no stimulation. When painful heat stimulation was unexpected, there was increased FMRI signal intensity in areas of the hippocampus, superior frontal gyrus, cerebellum, and superior parietal gyrus that was not found with mismatch between expectation and delivery of nonpainful warmth stimulation. When painful heat stimulation was unexpectedly omitted, the FMRI signal intensity decreased in the left superior parietal gyrus and increased in the other regions. These contrasting activation patterns correspond to two different mismatch concepts in theories of associative learning (Rescorla-Wagner, temporal difference vs. Pearce-Hall, Mackintosh). Searching for interventions to specifically modulate activation of these brain regions therefore offers an approach to identifying new treatments for chronic pain, which often has a substantial associative learning component.

2014

This article reviews situations in which stimuli produce an increase or a decrease in nociceptive responses through basic associative processes and provides an associative account of such changes. Specifically, the literature suggests that cues associated with stress can produce conditioned analgesia or conditioned hyperalgesia, depending on the properties of the conditioned stimulus (e.g., contextual cues and audiovisual cues vs. gustatory and olfactory cues, respectively) and the proprieties of the unconditioned stimulus (e.g., appetitive, aversive, or analgesic, respectively). When such cues are associated with reducers of exogenous pain (e.g., opiates), they typically increase sensitivity to pain. Overall, the evidence concerning conditioned stress-induced analgesia, conditioned hyperalagesia, conditioned tolerance to morphine, and conditioned reduction of morphine analgesia suggests that selective associations between stimuli underlie changes in pain sensitivity. Keywords pain; analgesia; hyperalgesia; morphine tolerance; conditioning Pavlov (1927) observed that pairing an initially innocuous stimulus (i.e., conditioned stimulus, CS) with a biologically relevant stimulus (i.e., unconditioned stimulus, US) caused subsequent presentations of the CS to elicit a conditioned response (CR) that is usually similar to the unconditioned response (UR) evoked by the biologically relevant stimulus. This associative process is widely known as classical or Pavlovian conditioning, and it is thought to play an important role in the modulation of pain sensitivity (e.g., Flor, 2000). Our operational definition of pain sensitivity includes diverse dependent variables utilized in experiments using humans and animals to assess how Pavlovian conditioning changes sensitivity to painful stimulation (the various measures used to assess pain are summarized in Table 1). Although most definitions of pain incorporate a subjective aspect, our working definition of pain here refers to objective nociceptive responses, which allows the incorporation of diverse experimental preparations and species into the discussion. Here we review experimental evidence involving classical conditioning preparations that produce a

The journal of pain : official journal of the American Pain Society, 2016

A classical conditioning framework is often used for clinical reasoning about pain that persists after tissue healing. However, experimental studies demonstrating classically conditioned pain in humans are lacking. The current study tested whether non-nociceptive somatosensory stimuli can come to modulate pain threshold after being paired with painful nociceptive stimuli in healthy humans. We used a differential simultaneous conditioning paradigm in which one non-painful vibrotactile conditioned stimulus (CS+) was simultaneously paired with an unconditioned painful laser stimulus (US), while another vibrotactile stimulus (CS-) was paired with a non-painful laser stimulus. After acquisition, at-pain-threshold laser stimuli were delivered simultaneously with a CS+ or CS- vibrotactile stimulus. The primary outcome was the percentage of at-threshold laser stimuli that were reported as painful. The results were as expected: after conditioning, at-threshold laser trials paired with the CS...

Experimental brain research, 2022

Innocuous cues that become associated with pain can enhance pain. This is termed classically conditioned hyperalgesia. The size of this effect varies under different conditions. We aimed to test whether the sensitising effect of pain-associated cues depends on the intensity of the paired test stimulus. To do this, two virtual reality environments were paired with either painful or non-painful vibrotactile stimuli in a counterbalanced fashion. The differential effect of the two environments was evaluated using pain intensity ratings of paired electrocutaneous test stimuli at three different intensity levels. Forty healthy participants were included in the study; 30 participants experienced sufficient pain during the learning phase and were included in the main analysis. An effect of environment (p = 0.014) and interaction between environment and test stimulus intensity was found (p = 0.046). Only the most intense test stimulus was modulated by environment. While the effect was small,...

Physical Therapy Reviews, 2014

Background: Associative learning is the theory that two stimuli can be paired to produce similar behavioral responses. In this model, a previously innocuous stimulus can become paired with a noxious stimulus to a point that this previously innocuous stimulus can result in the perception of pain. Objectives: This review discusses concepts related to neural activation and structural alterations in the presence of both chronic pain and post-traumatic stress disorder (PTSD). The role of associative learning and protective memory-based behavioral responses in the perception of pain is explored to provide a framework to inform clinical management of individuals with chronic pain and will be linked to the presence of actual or perceived threat or fear. Major Findings: Current research demonstrates that in individuals with chronic pain, cortical and subcortical processing of information shifts from normal nocioceptive processing areas to the medial prefrontal, anterior cingulate, and insular cortices, as well as the hippocampus (Hip) regions, all of which also show dysregulation, signs of gray matter atrophy, and changes in epigenetic coding. Because these regions are involved in memory, emotional processing, learning, and conditioning, it is reasonable to suggest that associative learning may be involved in the processing of both pain and PTSD. Conclusions: Clinically, rehabilitation paradigms that incorporate early intervention, positive expectation, therapeutic neuroscience education, visual imagery, movement retraining, and manual therapy all have the potential to change not only pain behavior but also the neural circuitry, epigenetic coding, and cortical morphology underlying chronic pain.