Electrocutaneous Stimuli Research Articles

Inhibition of Serotonin Reuptake in the Medial Prefrontal Cortex during Acquisition of a Condition Reflex Fear Reaction Promotes Formation of Generalized Fear

Intracerebral microdialysis studies of Sprague–Dawley rats showed that acquisition of a conditioned reflex fear reaction (combination of a conditioned sound signal CS+ and an unavoidable electrocutaneous stimulus) was accompanied by an increase in the level of extracellular serotonin in the medial prefrontal cortex. Administration of the selective serotonin transporter inhibitor fluoxetine (1 μM) into the medial prefrontal cortex during acquisition of the conditioned reflex fear reaction magnified the increase in extracellular serotonin in these structures seen during this test and, secondly, strengthened freezing of the animals at 1 day (the measure of fear) in response to the differential signal CS–, not associated with pain stimulation (test for generalization of fear), but had no effect on freezing in the same animals in response to the conditioned stimulus CS+, previously combined with pain stimulation (test for expression of the fear reaction). These data provide the first evidence that stimulation of the serotoninergic system of the medial prefrontal cortex during acquisition of a condition reflex fear reaction promotes subsequent generalization of this conditioned reflex reaction without affecting its formation.

Categorical interoception and the role of threat

Interoceptive fears and biased interoception are important characteristics of somatic symptom disorders. Categorization of interoceptive sensations impacts perception of their intensity and unpleasantness. In this study we investigated whether making interoceptive categories threat-relevant further biases interoception of individual sensations compared to safe categories. Either a category containing low- or high-intensity stimuli was made threat-relevant by instructing (and occasionally experiencing) that interoceptive sensations could be followed by an unpredictable electrocutaneous stimulus. We replicated that categorization had a profound impact on perceived interoceptive sensations, with stimuli within categories being perceived as more similar than equidistant stimuli at the category border. We found some evidence for the impact of threat on perceived characteristics of stimuli (with the direction of these effects depending on whether interoceptive stimuli of low or high intensity were threat-relevant), but not for altered categorical choice behaviour. These results imply that the perception of respiratory stimuli is influenced strongly by top-down processes such as categorization, and suggest that interoceptive processing may flexibly adapt to contextual factors such as threat in healthy individuals. However, inflexible responding to repeated and/or severe threat to the internal body may compromise accurate interoception and may result in interoceptive illusions contributing to medically unexplained symptoms and syndromes.

Activation of c-Fos Expression in the Retrosplenial Cortex but Not the Hippocampus Accompanies Formation of an Association between the Context and the Unconditioned Stimulus and Its Subsequent Retrieval in Mice

Identification of the neural mechanisms of associative memory is one of the fundamental tasks in neuroscience. We report here use of a model of associative learning in mice in which formation of a memory of a neutral context and subsequent association of transient presentation of this context with an unconditioned electrocutaneous stimulus (footshock) were separated in time. This provided for studies of relationship between different stages in the formation of this memory and protein synthesis and allowed us to study genomic activation of various brain structures during association and the memory of the context of the footshock. These studies showed that blockade of protein synthesis both during exploration of the novel context and during application of immediate footshock in an already familiar context impaired conditioned reflex freezing to this context. The association of the memory trace of the context of the footshock retrieved in response to a reminder was accompanied by activation of the expression of transcription factor c-Fos in the retrosplenial cortex. The retrosplenial cortex was also specifically activated by subsequent retrieval of the associative memory of the context. This activation was not seen in mice with impaired memory. No such differences were seen in the hippocampus, where activation of c-Fos expression occurred in relation to exploration of the novel context and not its association with the footshock. These results provide evidence that the retrosplenial cortex may be part of the neocortex supporting formation of associations between context and aversive unconditioned stimuli.

The relationship between pain-induced autonomic arousal and perceived duration.

Emotional distortions of the perceived duration of events are often explained in terms of increases and decreases in arousal. While this explanation is theoretically plausible, there is a lack of evidence for a direct relationship between physiological arousal and perceived duration. The aim of the current study was to investigate whether physiological arousal, defined by autonomic nervous system (ANS) activity is directly related to perceived duration. In two experiments we measured skin conductance level (SCL) and high frequency heart rate variability (HF HRV) during verbal estimation tasks. In Experiment 1, participants estimated the duration of electro-cutaneous stimuli previously rated as inducing no pain, low pain and high pain. High intensity stimuli were perceived as lasting for longer than low intensity stimuli, and these changes in duration estimation were associated with changes in ANS activity. In Experiment 2, participants estimated the duration of a neutral visual stimulus while experiencing different intensities of background thermal pain (no pain, low pain, and high pain), to determine whether task-irrelevant arousal also affects time perception. Duration estimations for the neutral stimulus did not increase with pain intensity despite significant increases in SCL. Furthermore, there was no association between ANS activity and time estimation in Experiment 2. These findings suggest that the relationship between physiological arousal and time perception is more complex than previously described. While physiological arousal can influence the perceived duration of events, it appears to have a greater capacity to do so when the to-be-timed stimulus is itself the source of arousal. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Changes in Pain-Related Fear and Pain When Avoidance Behavior is no Longer Effective

Avoidance is considered key in the development of chronic pain. However, little is known about how avoidance behavior subsequently affects pain-related fear and pain. We investigated this using a robotic arm reaching avoidance task. In a between-subjects design both Experimental Group (n = 30) and Yoked Control Group (n = 30) participants perform either of 3 movement trajectories (T1–T3) to reach a target location. During acquisition, only participants of the Experimental Group could partially or fully avoid a painful electrocutaneous stimulus by choosing the intermediate trajectory (T2; 50% reinforcement) or the longest trajectory (T3; 0% reinforcement) versus the shortest trajectory (T1: 100% reinforcement). After acquisition, contingencies changed (all trajectories 50% reinforced), and the acquired avoidance behavior no longer effectively prevented pain from occurring. The Yoked Control Group received the same reinforcement schedule as the Experimental Group irrespective of their behavior. When avoidance behavior became ineffective for the Experimental Group, pain-related fear increased for the previously safe(r) trajectories (T2 and T3) and remained the same for T1, whereas pain threshold and tolerance declined. For the Yoked Group, pain-related fear increased for all trajectories. The Experimental Group persisted in emitting avoidance behavior following the contingency change, albeit at a lower frequency than during acquisition. PerspectiveResults indicate participants become more afraid of and sensitive to pain, when previously acquired avoidance is no longer effective. Also, participants continue to show avoidance behavior despite it being not adaptive anymore. These findings suggest that ineffective avoidance may play role in the maintenance and development of chronic pain.

Hide Your Pain: Social Threat Increases Pain Reports and Aggression, but Reduces Facial Pain Expression and Empathy

Earlier research studying the effects of social threat on the experience and expression of pain led to mixed results. In this study, female participants (N = 32) came to the lab with 2 confederates. Both confederates administered a total of 10 painful electrocutaneous stimuli to the participant. The framing of the administration was manipulated in a within-subjects design: In the low social threat condition the participant was told that the confederate could choose between 10 and 20 pain stimuli, thus they believed that this confederate chose to administer the minimum allowed number of pain stimuli. In the high social threat condition the confederate had a choice between 1 and 10 stimuli, thus they believed that this confederate chose to administer the maximum allowed number of stimuli. Participants reported on the intensity, unpleasantness, and threat value of the painful stimuli, and their facial expression was recorded. Moreover, aggression and empathy toward the confederates were assessed. As hypothesized, participants reported increased pain intensity, unpleasantness, and threat in the high social threat condition compared to the low social threat condition, but showed less facial pain expression. Finally, participants exhibited increased aggression and reduced empathy toward the confederate in the high social threat condition. PerspectiveSocial threat reduces painful facial expression, but simultaneously increases pain reports, leading to a double burden of the person in pain. Additionally, social threat affected social relationships by increasing aggression and reducing empathy for the other.

(265) The Relationship between Discrimination and Pain Tolerance and its Potential Mediation by Stress: Results from the Oklahoma Study of Native American Pain Risk (OK-SNAP)

Compared to other racial/ethnic minority groups, Native Americans (NAs) are more likely to report experiences of discrimination and also have the highest prevalence of pain conditions. Thus, there is a need to understand how and why these disproportionately high rates occur. Discrimination has been conceptualized within the biopsychosocial model as a chronic psychosocial stressor that can lead to dysfunction of regulatory processes, such as pain. A recent study found that perceived discrimination increased psychological distress that, in turn, led to increased chronic pain. To date, these relationships have not yet been evaluated in NAs. The present study examined perceived discrimination, stress, and pain tolerance in healthy, pain-free NAs (N=112) and NHWs (N=128). Discrimination was measured with the Everyday Discrimination Scale (EDS), stress was measured with the Perceived Stress Scale (PSS), and pain tolerance was measured in reaction to cold, heat, electrocutaneous, and ischemia pain stimuli. Results indicated NAs experienced more discrimination than NHWs (p

Modulating pain thresholds through classical conditioning.

BackgroundClassical conditioning has frequently been shown to be capable of evoking fear of pain and avoidance behavior in the context of chronic pain. However, whether pain itself can be conditioned has rarely been investigated and remains a matter of debate. Therefore, the present study investigated whether pain threshold ratings can be modified by the presence of conditioned non-nociceptive sensory stimuli in healthy participant.MethodsIn 51 healthy volunteers, pain threshold to electrocutaneous stimuli was determined prior to participation in a simultaneous conditioning paradigm. Participants underwent an acquisition phase in which one non-painful vibrotactile stimulus (CS+) was repeatedly paired with a painful electrocutaneous stimulus, whereas a second vibrotactile stimulus of the same quality and intensity (CS−) was paired with a non-painful electrocutaneous stimulus. Stimulation was provided on the lower back with close proximity between the conditioned stimulus and the unconditioned stimulus. In the test phase, electrocutaneous stimuli at the individually-set threshold intensity were simultaneously delivered together with either a CS+ or CS−. Pain intensity ratings were obtained after each trial; expectancy ratings were obtained after each block. The primary outcome was the percentage of test stimuli that were rated as painful.ResultsTest stimuli were more likely to be rated as painful when they were paired with the CS+ than when they were paired with the CS−. This effect was not influenced by contingency awareness, nor by expectancies or mood states.DiscussionThe findings support the notion that the judgement of an event being painful or non-painful can be influenced by classical conditioning and corroborate the possible role of associative learning in the development and maintenance of chronic pain.

Biases in tactile localization by pointing: compression for weak stimuli and centering for distributions of stimuli.

Weak electrocutaneous stimuli applied to the forearm are erroneously localized toward its middle (Steenbergen P, Buitenweg JR, Trojan J, Veltink PH. Exp Brain Res 232: 597-607, 2014). We asked whether mechanical touch stimuli exhibit a similar bias and whether the bias is toward the middle of the forearm or toward the middle of the recent stimulus distribution. In experiments 1 and 2, participants ( n = 12 and n = 10) localized by pointing von Frey filaments applied to four locations on the dorsal forearm. Individually adjusted weak and strong stimuli ( experiment 1) or two levels of strong stimuli ( experiment 2) were presented in single sessions in random order. Weaker stimuli were localized with greater variability than the strong, with compression toward the middle of the forearm. Responses to the two levels of strong stimuli did not differ. In experiment 3, participants ( n = 16) were presented two spatially offset stimulus distributions (8 cm center-to-center), each offset from the forearm middle, on 2 different days. Out of four target locations comprising each distribution, two were shared. Responses to weak stimuli were compressed compared with responses to strong stimuli. Importantly, biases for the common targets had opposite directions, each being toward the middle of the distribution within which targets were presented. Responses to strong stimuli also exhibited a distribution-dependent bias, a 2-cm overall shift across the forearm midpoint. We conclude that touch localization is subject to intensity-dependent biases determined by the recent history of stimulation and possibly also by the available or perceived response space. NEW & NOTEWORTHY Recent findings show that weak electrical stimuli applied to the forearm are mislocalized toward the forearm middle, relative to strong stimuli. We found that weak mechanical stimuli are similarly mislocalized. The bias changed if, as a group, stimuli were not centered on the forearm middle: weak stimuli gravitated toward the center of prior stimulation. Localization of strong stimuli was also biased, consistent with the tendency to center responses within the available response space.

The Influence of Pain-Related Expectations on Intensity Perception of Nonpainful Somatosensory Stimuli.

The extent to which pain-related expectations, known to affect pain perception, also affect perception of nonpainful sensations remains unclear, as well as the potential role of unpredictability in this context. In a proprioceptive fear conditioning paradigm, various arm extension movements were associated with predictable and unpredictable electrocutaneous pain or its absence. During a subsequent test phase, nonpainful electrocutaneous stimuli with a high or low intensity were presented during movement execution. We used hierarchical drift diffusion modeling to examine the influence of expecting pain on the perceptual decision-making process underlying intensity perception of nonpainful sensations. In the first experiment (n = 36), the pain stimulus was never presented during the test phase after conditioning. In the second experiment (n = 39), partial reinforcement was adopted to prevent extinction of pain expectations. In both experiments, movements that were associated with (un)predictable pain led to higher pain expectancy, self-reported fear, unpleasantness, and arousal as compared with movements that were never paired with pain (effect sizes η2 ranging from 0.119 to 0.557; all p values < .05). Only in the second experiment-when the threat of pain remained present-we found that the expectation of pain affected decision making. Compared with the no pain condition, an a priori decision-making bias toward the high-intensity decision threshold was found with the strongest bias during unpredictable pain (effect sizes η2 ranging from 0.469 to 0.504; all p-values < .001). Thus, the expectation of pain affects inferential processes not only for subsequent painful but also for nonpainful bodily stimuli, with unpredictability moderating these effects, and only when the threat of pain remains present due to partial reinforcement.

Winning or not losing? The impact of non-pain goal focus on attentional bias to learned pain signals.

Background and aims Insights into the nature of cognitive bias, including attentional bias to threat signals, are considered pivotal to understanding (chronic) pain and related distress. It has been put forward that attention to pain-related threat is normally dynamic and relates to the motivational state of the individual. In this experiment we aimed (i) to replicate the finding that attentional bias for pain signals in healthy participants can be reduced when a non-pain goal is pursued, and (ii) to extend this finding by taking into account the outcome focus of the non-pain goal. We hypothesised that the reduction in attentional bias for pain signals by concurrent non-pain goal pursuit would be stronger with non-pain prevention goals than with promotion goals. Methods Healthy university students performed an attentional bias task (i.e. spatial cueing task) containing visual cues that signalled the possible occurrence of a painful stimulus (electrocutaneous stimulus at tolerance level) or its absence, in combination with a non-pain goal task (i.e. digit naming task). The non-pain goal was either related to acquiring a positive outcome (gaining money depending on digit-naming performance; promotion goal group, n=31) or related to avoiding a negative outcome (losing money; prevention goal group, n=31). A standard attentional bias task served as the control condition (control group, n=31). Results Spatial cueing effects were larger for pain cues than for no-pain cues, indicating attentional bias for pain signals. The pattern of results suggests that this effect was indeed reduced in the goal groups as compared to the control group, but there was no significant group difference. Conclusions We found no statistically-significant evidence for the impact of non-pain goal pursuit or outcome focus on pain-related attentional bias. At best, there were indications of a reduced attentional bias for pain signals with non-pain goal pursuit that was either promotion- or prevention focused. Implications These data add to the small but growing body of literature on the assumed relevance of motivational context in explaining variations in attentional bias. The results trigger new questions on the nature and assessment of pain-related attentional bias, and more specifically attentional bias for fear-conditioned pain signals (versus safety signals), from a motivational perspective.

Beyond Extinction: Prolonged Conditioning and Repeated Threat Exposure Abolish Contextual Renewal of Fear-Potentiated Startle Discrimination but Leave Expectancy Ratings Intact.

Extinction treatments decrease fear via repeated exposures to the conditioned stimulus (CS) and are associated with a return of fear. Alternatively, fear can be reduced via reductions in the perceived intensity of the unconditioned stimulus (US), e.g., through repeated exposures to the US. Promisingly, the few available studies show that repeated US exposures outperform standard extinction. US exposure treatments can decrease fear via two routes: (1) by weakening the CS–US association (extinction-like mechanism), and/or (2) by weakening the subjective US aversiveness (habituation-like mechanism). The current study further investigated the conditions under which US exposure treatment may reduce renewal, by adding a group in which CS–US pairings continued following fear acquisition. During acquisition, participants learned that one of two visual stimuli (CS+/CS−) predicted the occurrence of an aversive electrocutaneous stimulus (US). Next, the background context changed and participants received one of three interventions: repeated CS exposures, (2) repeated US exposures, or (3) continued CS–US pairings. Following repeated CS exposures, test presentations of the CSs in the original conditioning context revealed intact CS+/CS− differentiation in the fear-potentiated startle reflex, while the differentiation was abolished in the other two groups. Differential US expectancy ratings, on the other hand, were intact in all groups. Skin conductance data were inconclusive because standard context renewal following CS exposures did not occur. Unexpectedly, there was no evidence for a habituation-like process having taken place during US exposures or continued CS–US pairings. The results provide further evidence that US exposures outperform the standard extinction treatment and show that effects are similar when US exposures are part of CS–US pairings.

Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes.

Background: Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient endogenous pain modulation (EPM), as well as elevated levels of negative affectivity (NA) and high comorbidity with depression and reduced resting heart rate variability (HRV) compared to healthy controls (HC). The goals of this study were (1) to replicate these findings and (2) to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS). Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD) in rest, a vagally mediated time domain measure of HRV.Methods: Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency. Participants rated the painfulness of electrocutaneous stimuli (of individually calibrated intensity) on the ankle before (baseline phase), during (counter-irritation phase) and after (recovery phase) the application of a cold pain stimulus on the forearm. A larger reduction in pain in the counter-irritation phase compared to the baseline phase reflects a more efficient EPM.Results: In contrast to our expectations, there was no difference between pain ratings in the baseline compared to counter-irritation phase for both patients and HC. Therefore, reliable conclusions on the moderating effect of NA, depression, and RMSSD could not be made. Surprisingly, patients reported more pain in the recovery compared to the counter-irritation and baseline phase, while HC did not. This latter effect was more pronounced in patients with comorbid depression, patients who rated the painfulness of the counter-irritation stimulus as high and patients who rated the painfulness of the electrocutaneous stimuli as low. We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients. Therefore, no valid conclusions on the association between RMSSD, depression, NA and EPM efficiency can be drawn from this study. Possible reasons for the lack of the counter-irritation effect are discussed.

Quantitative Evaluation of Pain during Electrocutaneous Stimulation using a Log-Linearized Peripheral Arterial Viscoelastic Model

In clinical practice, subjective pain evaluations, e.g., the visual analogue scale and the numeric rating scale, are generally employed, but these are limited in terms of their ability to detect inaccurate reports, and are unsuitable for use in anesthetized patients or those with dementia. We focused on the peripheral sympathetic nerve activity that responds to pain, and propose a method for evaluating pain sensation, including intensity, sharpness, and dullness, using the arterial stiffness index. In the experiment, electrocardiogram, blood pressure, and photoplethysmograms were obtained, and an arterial viscoelastic model was applied to estimate arterial stiffness. The relationships among the stiffness index, self-reported pain sensation, and electrocutaneous stimuli were examined and modelled. The relationship between the stiffness index and pain sensation could be modelled using a sigmoid function with high determination coefficients, where R2 ≥ 0.88, p < 0.01 for intensity, R2 ≥ 0.89, p < 0.01 for sharpness, and R2 ≥ 0.84, p < 0.01 for dullness when the stimuli could appropriately evoke dull pain.

Effects of activity interruptions by pain on pattern of activity performance - an experimental investigation.

Suspending an ongoing activity with the intention to resume it again later is a natural response to pain. This response facilitates coping with the pain, but it may also have negative consequences for the resumption and performance of the activity. For example, people with pain problems are often forced to take a break from doing their household chores because of their pain. They might delay resuming their chore, eventually needing longer time to finish it. We investigated how activity interruptions by pain influence the pattern of subsequent activity performance. We expected that when an activity is interrupted by pain (compared to non-pain), people spend longer time away from the activity, need longer time to complete it, and are less motivated to perform it. Sixty healthy volunteers performed an ongoing task that required them to make joystick movements in different directions according to a specific rule. Occasionally, participants received either a painful electrocutaneous stimulus or a non-painful and non-aversive auditory stimulus (between-subjects) as an interruption cue. The interruption cue was followed by the temporary suspension of the ongoing task and the initiation of a different activity (interruption task). The latter required the categorization of cards and had a maximum duration, but participants could also stop it earlier by pressing a button. We measured time away from the (interrupted) ongoing task, total time to complete the ongoing task (including the interruptions) and self-reported motivation to perform both the ongoing as well as the interruption task. Groups did not differ in the time away from the ongoing task, total time to complete the ongoing task, or self-reported motivation to perform the two tasks. Activity interruptions by pain did not impair the pattern of activity performance more than activity interruptions by non-pain. Potential explanations and suggestions for future research are discussed. Interrupting ongoing activities is a common response to pain. However, activity interruptions by pain do not appear to influence the pattern of activity performance in a different way than activity interruptions by pain-irrelevant external stimuli.

The Influence of Social Threat on Pain, Aggression, and Empathy in Women

Only one published study has investigated the effect of a threatening social context on the perception and expression of pain, showing that social threat leads to increased pain reports but reduced nonverbal pain expression. The current study aimed to replicate and extend these findings to further explore the effects of a threatening social context. Healthy, female participants (N = 71) received 10 electrocutaneous stimuli delivered by a confederate. They were led to believe that the confederate was requested to administer 10 painful stimuli (control group) or that the confederate deliberately chose to deliver 10 painful stimuli when given the choice to deliver between 1 to 10 painful stimuli (social threat group). Self-reported pain intensity, unpleasantness, threat value of pain, and painful facial expression were assessed. Additionally, empathy and aggression toward the confederate were investigated. Social threat did not affect painful facial expression or self-reported pain intensity, but led to increased aggression toward the confederate. Moreover, perceived social threat predicted the threat value of pain and reduced empathy toward the confederate. We were not able to replicate the previously reported dissociation between pain reports and pain expression as a result of social threat. However, social threat was associated with an increased threat value of pain, increased aggression, and reduced empathy. PerspectiveA threatening social context affects how threatening pain is perceived and has interpersonal consequences such as increased aggression and reduced empathy, thereby creating a double burden on the individual suffering from pain.

Subjective utility moderates bidirectional effects of conflicting motivations on pain perception.

Minimizing pain and maximizing pleasure are conflicting motivations when pain and reward co-occur. Decisions to prioritize reward consumption or pain avoidance are assumed to lead to pain inhibition or facilitation, respectively. Such decisions are a function of the subjective utility of the stimuli involved, i.e. the relative value assigned to the stimuli to compare the potential outcomes of a decision. To test perceptual pain modulation by varying degrees of motivational conflicts and the role of subjective utility, we implemented a task in which healthy volunteers had to decide between accepting a reward at the cost of receiving a nociceptive electrocutaneous stimulus or rejecting both. Subjective utility of the stimuli was assessed by a matching task between the stimuli. Accepting reward coupled to a nociceptive stimulus resulted in decreased perceived intensity, while rejecting the reward to avoid pain resulted in increased perceived intensity, but in both cases only if a high motivational conflict was present. Subjective utility of the stimuli involved moderated these bidirectional perceptual effects: the more a person valued money over pain, the more perceived intensity increased or decreased. These findings demonstrate pain modulation when pain and reward are simultaneously present and highlight the importance of subjective utility for such modulation.

Preliminary Evidence for Training-Induced Changes of Morphology and Phantom Limb Pain.

The aim of this study was to investigate whether a special prosthetic training in phantom limb pain patients aimed at increasing the functional use of the prosthesis leads to neural morphological plasticity of brain structures and a reduction in phantom limb pain. For chronic pain disorders, it was shown that morphological alterations due to pain might become at least partially reversed by pain therapies. Phantom limb pain is a chronic pain disorder that is frequently followed by neural plasticity of anatomical brain structures. In our study, 10 patients with amputation of the upper limb participated in a two-week training with a myoelectric prosthesis with somatosensory feedback. Grip strength was fed back with electrocutaneous stimulus patterns applied to the stump. Phantom limb pain was assessed before and after the two-week training. Similarly, two T1 weighted MRI scans were conducted for longitudinal thickness analyses of cortical brain structures. As result of this treatment, patients experienced a reduction in phantom limb pain and a gain in prosthesis functionality. Furthermore, we found a change of cortical thickness in small brain areas in the visual stream and the post-central gyrus ipsilateral to the amputation indicating morphological alterations in brain areas involved in vision and pain processing.

Estimation and Identifiability of Model Parameters in Human Nociceptive Processing Using Yes-No Detection Responses to Electrocutaneous Stimulation.

Healthy or pathological states of nociceptive subsystems determine different stimulus-response relations measured from quantitative sensory testing. In turn, stimulus-response measurements may be used to assess these states. In a recently developed computational model, six model parameters characterize activation of nerve endings and spinal neurons. However, both model nonlinearity and limited information in yes-no detection responses to electrocutaneous stimuli challenge to estimate model parameters. Here, we address the question whether and how one can overcome these difficulties for reliable parameter estimation. First, we fit the computational model to experimental stimulus-response pairs by maximizing the likelihood. To evaluate the balance between model fit and complexity, i.e., the number of model parameters, we evaluate the Bayesian Information Criterion. We find that the computational model is better than a conventional logistic model regarding the balance. Second, our theoretical analysis suggests to vary the pulse width among applied stimuli as a necessary condition to prevent structural non-identifiability. In addition, the numerically implemented profile likelihood approach reveals structural and practical non-identifiability. Our model-based approach with integration of psychophysical measurements can be useful for a reliable assessment of states of the nociceptive system.

Behavioral Inhibition and Behavioral Activation are Related to Habituation of Nociceptive Flexion Reflex, but Not Pain Ratings.

Using repeated NFR stimulation, this study showed that most participants exhibited NFR habituation and pain sensitization; however, a substantial subgroup showed an opposite pattern of pain habituation (25.0%) and NFR sensitization (31.4%). Further, NFR habituation was moderated by individual differences in behavioral activation and behavioral inhibition.