Enhanced Itch Intensity Is Associated with Less Efficient Descending Inhibition Processing for Itch But Not Pain Attenuation in Chronic Dermatology Patients.

OBJECTIVES: The study aims were 1) to investigate the direction of mutual inhibitory pathways on itch intensity by utilizing conditioned pain modulation paradigms for pain and itch attenuation and 2) to explore whether itch severity is affected by the individual pain sensitivity profile, as well as pain scores reported during the tests and the past week. DESIGN: Cross-sectional. SETTING: Testing was conducted at the Department of Dermatology, Rambam Health Care Campus. SUBJECTS: Forty patients suffering from chronic skin disorders associated with itch and treated in the Dermatology Clinic at Rambam Health Care Campus participated in the study. METHODS: Efficacy of descending inhibition was evaluated by two conditioned pain modulation (CPM) paradigms: by pruriception (CPMItch) induced by cold and heat as counterstimuli to inhibit itch intensity and by nociception (CPMPain). Severity and interference of clinical pain were assessed using the Brief Pain Inventory (BPI). RESULTS: Robust CPMItch responses were obtained following the various noxious stimulations. No associations were observed between CPMPain and CPMItch, itch severity, skin disease severity, and clinical pain symptoms. According to the linear regression model, itch severity was independently associated with less efficient CPMItch (B = -0.750, P < 0.001) and more efficient CPMPain (B = 0.031, P = 0.016), which affects itch in opposing manners. CONCLUSIONS: Findings indicate that the intrinsic capacity to inhibit pain and itch by exposure to exogenous noxious stimuli autonomously affects itch intensity in an opposing manner. These findings may shed new light on the mutual mechanistic similarity and dissimilarity between pain and itch and their hierarchy.

Sex dimorphism in a mediatory role of the posterior midcingulate cortex in the association between anxiety and pain sensitivity.

Behavioral studies found greater pain sensitivity in females that vanishes fully or partially when controlling for the emotional state. Furthermore, pain-related brain activation hints at the role of limbic structures in sex differences in pain processing. We aimed to investigate the role of pain-related limbic structures in mediating the relation between subjects' affective state (i.e., anxiety) and pain. Contact heat-evoked potentials (CHEPs) were recorded in 26 healthy subjects (13 males) simultaneously with innocuous (42 °C) baseline and target noxious (52 °C) series of stimuli administered to the left non-dominant volar forearm. The N2 and P2 components were analyzed, and their generators' activity was estimated using standardized low-resolution brain electromagnetic tomography. Thereafter, structural equation modeling (SEM) was applied separately for females and males, examining the mediatory role of the CHEPs' limbic structures generators [posterior midcingulate cortex (pMCC), insula, amygdala, and hippocampus] in the anxiety-pain sensitivity association. Females exhibited greater P2 amplitudes that were highly associated with larger pMCC activity (r = 0.910, p < 0.001). This correlation was also evident in males, though with less strength (r = 0.578, p = 0.039). Moreover, the P2 amplitudes were associated both in females (r = 0.645, p = 0.017) and males (r = 0.608, p = 0.028) with the activity of the amygdala\hippocampus\insula. SEM revealed that the relationship between state anxiety and pain ratings was only in females fully mediated via the effect of the pMCC on the P2 amplitude. These findings suggest that sexual dimorphism in anxiety-related brain activity may explain the differences found in CHEPs and the sex-related association between anxiety and pain.

An Exploratory Study Testing Autonomic Reactivity to Pain in Women with Sensory Over-Responsiveness.

BACKGROUND: Difficulty modulating sensory input related to multi-sensory integration dysfunction, specifically the sensory over-responsive (SOR) type, is associated with psychological distress and hyperalgesia in children and adults. Scares reports suggest atypical autonomic nervous system (ANS) reactivity to innocuous sensory stimuli in children with SOR. Thus, the ANS may contribute to sensory stimuli responses and psychological distress. This exploratory study aimed to characterize the ANS reactivity to single and dual pain stimulation, and in relation to psychological distress in adults with SOR. METHODS: Healthy women with SOR (n = 9) vs. without SOR (n = 9) underwent two runs of single pain stimulation and a third run comprised of dual pain stimulation. Pain was self-rated, while heart rate variability was measured and analyzed in the time and frequency domains. In addition, questionnaires assessing anxiety and somatization were utilized. RESULTS: While controls demonstrated a vagal tone withdrawal (root mean square of successive differences in R-R-intervals; (RMSSD)) p = 0.029 from base-line to the third run, this was absent in the SOR group. However, no group differences were found in pain ratings. Furthermore, groups differed in the correlations between R-R mean and the level of both anxiety (p = 0.006) and somatization (p < 0.001); while in the SOR group, higher levels of anxiety and somatization correlated with shorter R-R intervals, the opposite was found in the control group. CONCLUSIONS: This is the first study to demonstrate in women with SOR atypical vagal tone reactivity to challenging pain load. Vagal tone reactivity is related to both pain ratings and psychological distress.

Development and preliminary validation of the focused analgesia selection test to identify accurate pain reporters.

Clinical trials of analgesics have been plagued with poor assay sensitivity due, in part, to variability in subjects' pain reporting. Herein, we develop and evaluate the focused analgesia selection test (FAST), a method to measure patients' pain reporting skills. Subjects with osteoarthritis of the hip, knee, and/or ankle with pain intensity of ≥3/10 on a 0-10 numerical rating scale were enrolled. Subjects underwent the FAST procedure, which consists of recording subjects' pain reports in response to repeated administration of thermal noxious stimuli of various intensities applied on the arm with the Medoc® Thermal Sensory Analyzer II. Subjects also rated non-noxious stimuli consisting of visual contrast rating. After performing an exercise task, subjects also rated clinical pain and were asked to report whether their pain had increased, decreased, or stayed the same. Overall, 88 subjects were enrolled, and 83 were included in the analyses. FAST's outcomes including the R2, intraclass correlation coefficient (ICC), and coefficient of variation (CoV) indicated that subjects' pain reporting skills were widely distributed. Higher FAST ICC significantly predicted greater changes in clinical pain following exercise (p=0.017), whereas the visual contrast test did not predict postexercise pain. FAST is the first method that measures subjects' pain reporting skills. Using FAST to enrich clinical trials with "good" pain reporters (with high FAST ICC) could increase assay sensitivity. Further evaluation of FAST is ongoing.

Bi-phasic activation of the primary motor cortex by pain and its relation to pain-evoked potentials - an exploratory study.

The primary motor cortex (M1) is a known target for brain stimulation aimed at pain alleviation in chronic pain patients, yet the mechanisms through which analgesia occurs, and the exact pain-motor interrelations are not fully understood. We used noxious contact heat evoked potentials (CHEPs) and cortical source analysis to further explore the relevance of M1 in pain processing. Twenty-four healthy young females received brief noxious heat stimuli to their left non-dominant volar forearm, simultaneously with CHEPs recordings. Thereafter, the pain-evoked activity of M1 and a control area in the occipital cortex (OC) was analyzed and estimated using sLORETA (standardized low-resolution brain electromagnetic tomography). This analysis revealed two phases of M1 pain-evoked activation (phase 1: the peak at 261.5±25.7ms; phase 2: the peak at 381.3±28.3ms). Canonical correlations revealed that M1, but not the OC, was the main factor contributing to the relation with the CHEPs components. In detail, the activity magnitude of M1 first and second phases was related to the N2 and P2 amplitude, respectively. The latency of the second phase was associated with both N2 and P2 latencies. In relation to pain, the latency of M1's first activity phase was positively correlated with pain ratings, suggesting pain interference to synchronized activity in M1. Our results confirm the established relevance of the primary motor cortex to pain processing.

Distinguishing Feigned From Sincere Performance in Psychophysical Pain Testing.

UNLABELLED: Self-report, the most widely used, gold standard measurement of pain, is crucial for pain research, diagnosis, and management. However, there are no accurate, reliable methods for detecting dishonesty in self-reports when there is incentive for pain deception. We introduce a novel approach to detecting pain deception by analyzing performance patterns of honest and dishonest psychophysical pain testing. Warmth sensation threshold (WST) and heat pain threshold (HPT) were measured in healthy individuals (N = 37) under 2 conditions: standard instruction (ie, provide sincere reports) and instructions to simulate intense pain (i.e., provide feigned reports) with the intention of deceiving. In the feigned compared with sincere condition, participants had significantly increased WST and decreased HPT. Repeatability and variability indices were indistinguishable between conditions. In a second, separate cohort (N = 24), measurements were repeated with the addition of a sensory interference to influence task performance. When sensory interference during HPT measurement was introduced, feigned pain reports had significantly higher variability and poorer repeatability compared with sincere reports and were distinguishable from sincere reports, with high sensitivity (83%) and specificity (84%). The statistical properties of psychophysical performance under sensory interference provide a method for identifying feigned performance and could be applied to evaluations of pain malingering. PERSPECTIVE: This article introduces a method to detect whether individuals are being dishonest in psychophysical pain testing. The method could help clinicians to detect chronic pain malingering in contexts in which there is incentive to deceive.

A dor como um problema psicofísico / Pain as a psychophysical problem

JUSTIFICATIVA E OBJETIVOS: A quantificação da dor enfrenta dificuldades especiais. Elas surgem devido à óbvia associação das sensações de dor com um conjunto de fatores emocionais, motivacionais e culturais. Apesar disso, a mensuração da dor é essencial para a avaliação eo tratamento dos seus efeitos. O objetivo deste estudo foi mostrar que os métodos psicofísicos podem ser adequadamente empregados para a mensuração, tanto da dor clínica quando da dor experimental.CONTEÚDO: Em adição, a metodologia pode ser útil para analisar os mecanismos da dor, a analgesia, os vieses metodológicos inerentes aos registros verbais da dor e dissociar os componentes sensoriais e cognitivos da sensação/percepção de dor.CONCLUSÃO: A metodologia psicofísica pode ser umamedida fidedigna e válida do quinto sinal vital, que é a dor,em todas as suas dimensões.

BACKGROUND AND OBJECTIVES: Pain quantification faces special difficulties. They appear due to the obvious association of pain to a set of emotional, motivational and cultural factors. However, pain measurement isessential to evaluate and treat its effects. This study aimedat showing that psychophysical methods might be adequately used to measure both clinical and experimental pain.CONTENTS: In addition, the methodology may be useful to analyze pain mechanisms, analgesia, methodological biases inherent to pain verbal records, and to dissociate sensory and cognitive components from pain sensation/perception.CONCLUSION: The psychophysical methodology may be a trustworthy and valid measurement of the fifth vital sign, which is pain, in all its dimensions.