Classically conditioned modulation of pain depends on stimulus intensity.

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, the results are consistent with the proposition that pain-associated cues may induce hyperalgesia to some degree, under certain conditions. In particular, results highlight the potential relevance of stimulus intensity during and after the initial painful experience. Further attention is needed to comprehensively understand the variables that impact classically conditioned hyperalgesia.

The iSTOPP study: Protocol for a proof-of-concept randomised clinical trial of sensory discrimination training in people with persistent neck pain.

BACKGROUND: Neck pain can be associated with a reduction in tactile acuity that is thought to reflect disrupted sensory processing. Tactile acuity training may normalise sensory processing and improve symptoms. This proof-of-concept trial will assess the feasibility of a novel tactile acuity training method and whether this intervention improves tactile acuity in people with persistent neck pain. METHODS: and analysis: In this two-arm randomised clinical proof-of-concept trial we will recruit participants with neck pain receiving usual care physiotherapy in a secondary outpatient healthcare setting. Thirty-six participants will be randomised 2:1 to receive four weeks of either tactile acuity training using the Imprint Tactile Acuity Device (iTAD) or a placebo intervention, in addition to usual care. The placebo intervention will consist of a de-activated TENS machine (iTENS) said to deliver a sub-threshold inhibitory therapy. Outcomes will be assessed at baseline, mid-treatment, and at 5-weeks and 2-months follow-up. The primary outcome tactile acuity will be evaluated using the two-point discrimination test and locognosia tests. Feasibility will be informed by recruitment and attrition rates, adherence, credibility of the interventions, treatment satisfaction and blinding. Pain intensity and anatomical spread will be analysed as secondary outcomes. The effect of iTAD training on tactile acuity will be assessed using a 2 (Group: iTAD vs. iTENS) x 4 (Time: baseline, mid-treatment, 5-week and 2-month outcome assessment) mixed ANOVA. Secondary outcomes including pain and pain spread, will be analysed with a focus on informing sample size calculations in future trials. ETHICS AND DISSEMINATION: Risks associated with this study are minor. Usual care is not withheld, and participants consent to random allocation of either iTAD or iTENS. Potential benefits to participants include any benefit associated with the interventions and contributing to research that may assist people with chronic pain in the future. Trial results will be disseminated via academic journals and conference presentations. The study is approved by the Human Research Ethics Committee of Griffith University (2017/128).

Modernising tactile acuity assessment; clinimetrics of semi-automated tests and effects of age, sex and anthropometry on performance.

BACKGROUND: Reduced tactile acuity has been observed in several chronic pain conditions and has been proposed as a clinical indicator of somatosensory impairments related to the condition. As some interventions targeting these impairments have resulted in pain reduction, assessing tactile acuity may have significant clinical potential. While two-point discrimination threshold (TPDT) is a popular method of assessing tactile acuity, large measurement error has been observed (impeding responsiveness) and its validity has been questioned. The recently developed semi-automated 'imprint Tactile Acuity Device' (iTAD) may improve tactile acuity assessment, but clinimetric properties of its scores (accuracy score, response time and rate correct score) need further examination. AIMS: Experiment 1: To determine inter-rater reliability and measurement error of TPDT and iTAD assessments. Experiment 2: To determine internal consistencies and floor or ceiling effects of iTAD scores, and investigate effects of age, sex, and anthropometry on performance. METHODS: Experiment 1: To assess inter-rater reliability (ICC(2,1)) and measurement error (coefficient of variation (CoV)), three assessors each performed TPDT and iTAD assessments at the neck in forty healthy participants. Experiment 2: To assess internal consistency (ICC(2,k)) and floor or ceiling effects (skewness z-scores), one hundred healthy participants performed the iTAD's localisation and orientation tests. Balanced for sex, participants were equally divided over five age brackets (18-30, 31-40, 41-50, 51-60 and 61-70). Age, sex, body mass index (BMI) and neck surface area were assessed to examine their direct (using multiple linear regression analysis) and indirect (using sequential mediation analysis) relationship with iTAD scores. RESULTS: Mean ICC(2,1) was moderate for TPDT (0.70) and moderate-to-good for the various iTAD scores (0.65-0.86). The CoV was 25.3% for TPDT and ranged from 6.1% to 16.5% for iTAD scores. Internal consistency was high for both iTAD accuracy scores (ICC(2,6) = 0.84; ICC(2,4) = 0.86). No overt floor or ceiling effects were detected (all skewness z-scores < 3.29). Accuracy scores were only directly related to age (decreasing with increasing age) and sex (higher for men). DISCUSSION: Although reliability was similar, iTAD scores demonstrated less measurement error than TPDT indicating a potential for better responsiveness to treatment effects. Further, unlike previously reported for TPDT, iTAD scores appeared independent of anthropometry, which simplifies interpretation. Additionally, the iTAD assesses multiple aspects of tactile processing which may provide a more comprehensive evaluation of tactile acuity. Taken together, the iTAD shows promise in measuring tactile acuity, but patient studies are needed to verify clinical relevance.

Description and psychometric properties of a prototype to test tactile acuity in the neck.

BACKGROUND: Clinical tools assessing tactile acuity in people with persistent pain have limitations. Therefore, a novel and semi-automated tool was developed: The Imprint Tactile Acuity Device (iTAD). AIM: To describe the iTAD prototype and present the psychometric properties of its tactile acuity assessments: the localisation test, the orientation test and the overall score (mean of both tests). METHOD: A test-retest design with fifty healthy participants was used to assess intra-rater reliability (ICC(2.1)), internal consistency (ICC(2.4)) and measurement error (SEM) of the three assessments (0-100% accuracy scores each) performed at the neck. Using a known-group comparison design, balanced by age and sex, scores of thirty individuals with persistent neck pain were compared to thirty healthy controls to determine construct validity. RESULTS: The ICC(2,1) and ICC(2,4) were 0.60 and 0.78 for the localisation test, 0.66 and 0.77 for the orientation test, and 0.73 and 0.84 for the overall score. The SEMs were 9.0%, 8.1% and 6.0%, respectively. No fixed or proportional bias, or signs of heteroscedasticity were observed. Overall, no between group differences were observed (p = 0.49). In the male subgroup, however, the overall score was lower for people with neck pain than for healthy participants (mean difference (SE); 7.6% (2.5); p = 0.008). DISCUSSION: The tactile acuity assessments of the iTAD demonstrate moderate reliability and good internal consistency. Measurement errors appear comparable to currently preferred methods. Clear construct validity was not established, but results may be biased by design issues of the prototype. Taken together, the iTAD shows promise but further fine-tuning is needed.

Learning to predict pain: differences in people with persistent neck pain and pain-free controls.

BACKGROUND: Learning to predict threatening events enables an organism to engage in protective behavior and prevent harm. Failure to differentiate between cues that truly predict danger and those that do not, however, may lead to indiscriminate fear and avoidance behaviors, which in turn may contribute to disability in people with persistent pain. We aimed to test whether people with persistent neck pain exhibit contingency learning deficits in predicting pain relative to pain-free, gender-and age-matched controls. METHOD: We developed a differential predictive learning task with a neck pain-relevant scenario. During the acquisition phase, images displaying two distinct neck positions were presented and participants were asked to predict whether these neck positions would lead to pain in a fictive patient with persistent neck pain (see fictive patient scenario details in Appendix A). After participants gave their pain-expectancy judgment in the hypothetical scenario, the verbal outcome (PAIN or NO PAIN) was shown on the screen. One image (CS+) was followed by the outcome "PAIN", while another image (CS-) was followed by the outcome "NO PAIN". During the generalization phase, novel but related images depicting neck positions along a continuum between the CS+ and CS- images (generalization stimuli; GSs) were introduced to assess the generalization of acquired predictive learning to the novel images; the GSs were always followed by the verbal outcome "NOTES UNREADABLE" to prevent extinction learning. Finally, an extinction phase was included in which all images were followed by "NO PAIN" assessing the persistence of pain-expectancy judgments following disconfirming information. RESULTS: Differential pain-expectancy learning was reduced in people with neck pain relative to controls, resulting from patients giving significantly lower pain-expectancy judgments for the CS+, and significantly higher pain-expectancy judgments for the CS-. People with neck pain also demonstrated flatter generalization gradients relative to controls. No differences in extinction were noted. DISCUSSION: The results support the hypothesis that people with persistent neck pain exhibit reduced differential pain-expectancy learning and flatter generalization gradients, reflecting deficits in predictive learning. Contrary to our hypothesis, no differences in extinction were found. These findings may be relevant to understanding behavioral aspects of chronic pain.

The Course of Activities in Daily Living: Who Is at Risk for Decline after First Ever Stroke?

BACKGROUND: Stroke is not only an acute disease, but for the majority of patients, it also becomes a chronic condition. There is a major concern about the long-term follow-up with respect to activities of daily living (ADL) in stroke survivors. Some patients seem to be at risk for decline after a first-ever stroke. The purpose of this study was to determine the course of ADL from 3 months after the first-ever stroke and onward and identify factors associated with decline in ADL. METHODS: A systematic literature search of 3 electronic databases through June 2015 was conducted. Longitudinal studies evaluating changes in ADL from 3 months post stroke onward were included. Cohorts including recurrent strokes and transient ischemic attacks were excluded. Regarding the course of ADL, a meta-analysis was performed using random-effects model. A best evidence synthesis was performed to identify factors associated with decline in ADL. RESULTS: Out of 10,473 publications, 28 unique studies were included. A small but significant improvement in ADL was found from 3 to 12 months post stroke (standardized mean difference (SMD) 0.17 (0.04-0.30)), which mainly seemed to occur between 3 and 6 months post stroke (SMD 0.15 (0.05-0.26)). From 1 to 3 years post stroke, no significant change was found. Five studies found a decline in ADL status over time in 12-40% of patients. Nine factors were associated with ADL decline. There is moderate evidence for being dependent in ADL and impaired motor function of the leg. Limited evidence was found associated with insurance status, living alone, age ≥80, inactive state and having impaired cognitive function, depression and fatigue with decline in ADL. CONCLUSION: Although on an average patients do not seem to decline in ADL for up to 3 years, there is considerable variation within the population. Some modifiable factors associated with decline in ADL were identified. However, more research is needed before patients at risk of deterioration in ADL can be identified.

Psychologically induced cooling of a specific body part caused by the illusory ownership of an artificial counterpart.

The sense of body ownership represents a fundamental aspect of our self-awareness, but is disrupted in many neurological, psychiatric, and psychological conditions that are also characterized by disruption of skin temperature regulation, sometimes in a single limb. We hypothesized that skin temperature in a specific limb could be disrupted by psychologically disrupting the sense of ownership of that limb. In six separate experiments, and by using an established protocol to induce the rubber hand illusion, we demonstrate that skin temperature of the real hand decreases when we take ownership of an artificial counterpart. The decrease in skin temperature is limb-specific: it does not occur in the unstimulated hand, nor in the ipsilateral foot. The effect is not evoked by tactile or visual input per se, nor by simultaneous tactile and visual input per se, nor by a shift in attention toward the experimental side or limb. In fact, taking ownership of an artificial hand slows tactile processing of information from the real hand, which is also observed in patients who demonstrate body disownership after stroke. These findings of psychologically induced limb-specific disruption of temperature regulation provide the first evidence that: taking ownership of an artificial body part has consequences for the real body part; that the awareness of our physical self and the physiological regulation of self are closely linked in a top-down manner; and that cognitive processes that disrupt the sense of body ownership may in turn disrupt temperature regulation in numerous states characterized by both.