Beyond numbers: integrating qualitative analysis into quantitative sensory testing for neuropathic pain.

This article investigates the benefits of adopting qualitative and quantitative sensory testing (QQST) in sensory assessment, with a focus on understanding neuropathic pain. The innovative QQST method combines participant qualitative experiences with quantitative psychophysical measurements, offering a more varied interpretation of sensory abnormalities and normal sensory function. This article also explores the steps for the optimization of the method by identifying qualitative signs of sensory abnormalities and standardizing data collection. By leveraging the inherent subjectivity in the test design and participant responses, the QQST method contributes to a more holistic exploration of both normal and abnormal sensory experiences. This article positions the QQST approach as a foundational element within the Sensory Evaluation Network, uniting international experts to harmonize qualitative and quantitative sensory evaluation methods.

Trends in Brain Research: A Bibliometric Analysis.

BACKGROUND: Bibliometrics methods have allowed researchers to assess the popularity of brain research through the ever-growing number of brain-related research papers. While many topics of brain research have been covered by previous studies, there is no comprehensive overview of the evolution of brain research and its various specialties and funding practices over a long period of time. OBJECTIVE: This paper aims to (1) determine how brain research has evolved over time in terms of number of papers, (2) countries' relative and absolute positioning in terms of papers and impact, and (3) how those various trends vary by area. METHODS: Using a list of validated keywords, we extracted brain-related articles and journals indexed in the Web of Science over the 1991-2020 period, for a total of 2,467,708 papers. We used three indicators to perform: number of papers, specialization, and research impact. RESULTS: Our results show that over the past 30 years, the number of brain-related papers has grown at a faster pace than science in general, with China being at the forefront of this growth. Different patterns of specialization among countries and funders were also underlined. Finally, the NIH, the European Commission, the National Natural Science Foundation of China, the UK Medical Research Council, and the German Research Foundation were found to be among the top funders. CONCLUSION: Despite data-related limitations, our findings provide a large-scope snapshot of the evolution of brain research and its funding, which may be used as a baseline for future studies on these topics.

Clinical Characterization of Pediatric Erythromelalgia: A Single-Center Case Series.

Erythromelalgia is a descriptive term for severe burning pain and erythema in the distal extremities relieved by cold and exacerbated by heat. Pediatric case series to date are relatively small. We extracted and analyzed medical record data for 42 pediatric patients to describe clinical characteristics, associated conditions, and responses to treatments. Informed consent was obtained according to an IRB-approved protocol that included gene discovery. Three patients had confirmed Nav1.7 sodium channelopathies, with six additional patients under investigation with novel gene candidates. There was a female predominance (2.5:1), and the median onset age was 12 years (IQR = 3-14). Patients saw a median of three specialists (IQR = 2-3) for a diagnosis. The majority (90%) reported bilateral symptoms. Cooling methods usually provided partial relief, while heat and exercise exacerbated pain. No medication appeared to be consistently effective; commonly prescribed medications included sodium channel blockers (n = 37), topical analgesics (n = 26), gabapentin (n = 22), and aspirin (n = 15). Based on the currently published literature, we believe this cohort is the largest pediatric study of erythromelalgia to date. Many findings are consistent with those of previously published case series. Work is in progress to establish a prospective cohort and multi-center registry.

Validation of the Critical-Care Pain Observation Tool (CPOT) in pediatric patients undergoing orthopedic surgery.

Background: Postoperative pain cannot be measured accurately among many children with intellectual and developmental disabilities, resulting in underrecognition or delay in recognition of pain. The Critical-Care Pain Observation Tool (CPOT) is a pain assessment tool that has been widely validated in critically ill and postoperative adults. Aims: The objective of this study was to validate the CPOT for use with pediatric patients able to self-report and undergoing posterior spinal fusion surgery. Methods: Twenty-four patients (10-18 years old) scheduled to undergo surgery were consented to this repeated-measure, within-subject study. To examine discriminative and criterion validation, CPOT scores and patients' self-reports of pain intensity were collected prospectively by a bedside rater before, during, and after a nonnociceptive and nociceptive procedure on the day following surgery. Patients' behavioral reactions were video recorded at the bedside and retrospectively viewed by two independent video raters to examine interrater and intrarater reliability of CPOT scores. Results: Discriminative validation was supported with higher CPOT scores during the nociceptive procedure than during the nonnociceptive procedure. Criterion validation was supported with a moderate positive correlation between the CPOT scores and the patients' self-reported pain intensity during the nociceptive procedure. A CPOT cutoff score of ≥2 was associated with the maximum sensitivity (61.3%) and specificity (94.1%). Reliability analyses revealed poor to moderate agreement between bedside and video raters and moderate to excellent consistency within video raters. Conclusions: These findings suggest that the CPOT may be a valid tool to detect pain in pediatric patients in the acute postoperative inpatient care unit after posterior spinal fusion.

Contexte: La douleur postopératoire ne peut pas être mesurée avec précision chez de nombreux enfants atteints de déficience intellectuelle et développementale, entraînant ainsi une méconnaissance ou un retard dans la reconnaissance de la douleur. Le Critical-Care Pain Observation Tool (CPOT) est un outil d'évaluation de la douleur qui a été largement validé chez les adultes gravement malades et postopératoires.Objectifs: L'objectif de cette étude était de valider le CPOT pour une utilisation auprès de patients pédiatriques capables d'autoévaluation et subissant une chirurgie de fusion vertébrale postérieure.Méthodes: Dans le cadre d'une étude intra-sujet, un consentement à cette mesure répétée a été obtenu pour vingt-quatre patients (10­18 ans) devant subir une intervention chirurgicale. Pour examiner la validation discriminante et de critère, les scores CPOT et les autoévaluations des patients concernant l'intensité de la douleur ont été collectés de manière prospective par un évaluateur au chevet du patient avant, pendant et après une procédure non nociceptive et nociceptive le lendemain de la chirurgie. Les réactions comportementales des patients ont été enregistrées sur vidéo au chevet du patient et visionnées rétrospectivement par deux des évaluateurs vidéo indépendants pour examiner la fiabilité des scores CPOT inter-évaluateurs et intra-évaluateurs.Résultats: La validation discriminante a été confirmée par l'obtention de scores plus élevés à l'échelle CPOT pendant la procédure nociceptive que pendant la procédure non nociceptive. La validation de critère a été confirmée par une corrélation positive modérée entre les scores sur l'échelle CPOT et l'intensité de la douleur autoévaluée par les patients pendant la procédure nociceptive. Un score-seuil ≥ 2 sur l'échelle CPOT a été associé à la sensibilité et la spécificité maximales (61,3 % et 94,1 %, respectivement). Les analyses de fiabilité ont révélé une concordance faible à modérée entre les évaluateurs de chevet et les évaluateurs vidéo, et une cocordance modérée à excellente parmi les évaluateurs vidéo.Conclusions: Ces résultats indiquent que le CPOT peut être un outil valide pour détecter la douleur chez les enfants patients de l'unité de soins hospitaliers postopératoires aigus après une fusion rachidienne postérieure.

The Psychosocial Characteristics and Somatosensory Function of Children and Adolescents Who Meet the Criteria for Chronic Nociplastic Pain.

Purpose: Nociplastic pain distinguishes individuals with pain and hypersensitivity in body regions with apparently normal tissues, without any signs of neuropathy, but with contribution of central and/or peripheral sensitization. There is a lack of literature describing nociplastic pain in the pediatric population. The objective of this study was to investigate the differences between pediatric patients with nociplastic pain compared with patients with non-nociplastic pain. Patients and Methods: This study included 414 pediatric patients followed at an interdisciplinary centre for complex pain. All patients underwent an exhaustive pain assessment consisting of face-to-face interviews, validated self-report questionnaires and quantitative sensory testing. Recently established criteria for chronic nociplastic pain, and quantitative sensory testing was used to describe and stratify our cohort. Results: One hundred and sixty-five patients (40%) were stratified as having possible nociplastic pain and two hundred and forty-nine (60%) patients, as non-nociplastic pain. Patients with nociplastic pain displayed pain hypersensitivity in the region of pain, more symptoms of panic and social phobia, and worse sleep quality than patients with non-nociplastic pain. The proportion of patients achieving a meaningful clinical outcome after completion of their treatment (medications, physiotherapy, psychology, nursing, social worker, and/or interventional procedures) was lower in patients with nociplastic pain (62%) than those without nociplastic pain (86%). Conclusion: Our results suggest that patients who meet the criteria for nociplastic pain can be identified in a population of children and adolescents being treated in a center for complex pain. Combining screening with validated questionnaires and quantitative sensory testing facilitates the phenotyping and graded severity of patients with nociplastic pain in daily clinical practice.

Accurate classification of pain experiences using wearable electroencephalography in adolescents with and without chronic musculoskeletal pain.

Objective: We assessed the potential of using EEG to detect cold thermal pain in adolescents with and without chronic musculoskeletal pain. Methods: Thirty-nine healthy controls (15.2 ± 2.1 years, 18 females) and 121 chronic pain participants (15.0 ± 2.0 years, 100 females, 85 experiencing pain ≥12-months) had 19-channel EEG recorded at rest and throughout a cold-pressor task (CPT). Permutation entropy, directed phase lag index, peak frequency, and binary graph theory features were calculated across 10-second EEG epochs (Healthy: 292 baseline / 273 CPT epochs; Pain: 1039 baseline / 755 CPT epochs). Support vector machine (SVM) and logistic regression models were trained to classify between baseline and CPT conditions separately for control and pain participants. Results: SVM models significantly distinguished between baseline and CPT conditions in chronic pain (75.2% accuracy, 95% CI: 71.4%-77.1%; p < 0.0001) and control (74.8% accuracy, 95% CI: 66.3%-77.6%; p < 0.0001) participants. Logistic regression models performed similar to the SVM (Pain: 75.8% accuracy, 95% CI: 69.5%-76.6%, p < 0.0001; Controls: 72.0% accuracy, 95% CI: 64.5%-78.5%, p < 0.0001). Permutation entropy features in the theta frequency band were the largest contributor to model accuracy for both groups. Conclusions: Our results demonstrate that subjective pain experiences can accurately be detected from electrophysiological data, and represent the first step towards the development of a point-of-care system to detect pain in the absence of self-report.

Clusters of facilitatory and inhibitory conditioned pain modulation responses in a large sample of children, adolescents, and young adults with chronic pain.

Introduction: When investigating the role of facilitatory and inhibitory pain mechanisms such as conditioned pain modulation (CPM) and temporal summation of pain (TSP), it is important to take both into consideration in a single experimental model to provide the most information on subgroups of patients. Therefore, the objective of this study was to identify subgroups in a large population of pediatric patients with chronic pain based on their facilitatory and inhibitory pain mechanisms and compare them with control subjects. Methods: Five hundred twenty-one female subjects and 147 male subjects between 8 and 21 years old underwent a CPM assessment using a 2-minute tonic noxious heat stimulation as the test stimulus and a 2-minute cold-pressor task (CPT) (12°C) as the conditioning stimulus. Results: The best partition of clusters of patients was 3 clusters accounting for 27.15% of the total variation in the data. Cluster 1 (n = 271) was best characterized by high pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 2 (n = 186) was best characterized by low pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 3 (n = 151) was best characterized by high pain intensity during the CPT, presence of TSP during the test stimuli, and inefficient inhibitory CPM. Discussion: A single thermal CPM experimental design can identify combinations of facilitatory and inhibitory pain modulation responses. Findings from the current study add to the literature by describing different clinical phenotypes of central pain mechanisms of youth with chronic pain.

Phenotyping Chronic Musculoskeletal Pain in Male and Female Adolescents: Psychosocial Profiles, Somatosensory Profiles and Pain Modulatory Profiles.

PURPOSE: A major limitation in treatment outcomes for chronic pain is the heterogeneity of the population. Therefore, a personalized approach to the assessment and treatment of children and adolescents with chronic pain conditions is needed. The objective of the study was to subgroup pediatric patients with chronic MSK pain that will be phenotypically different from each other based on their psychosocial profile, somatosensory function, and pain modulation. PATIENTS AND METHODS: This observational cohort study recruited 302 adolescents (10-18 years) with chronic musculoskeletal pain and 80 age-matched controls. After validated self-report questionnaires on psychosocial factors were completed, quantitative sensory tests (QST) and conditioned pain modulation (CPM) were performed. RESULTS: Three psychosocial subgroups were identified: adaptive pain (n=125), high pain dysfunctional (n=115), high somatic symptoms (n=62). Based on QST, four somatosensory profiles were observed: normal QST (n=155), thermal hyperalgesia (n=98), mechanical hyperalgesia (n=34) and sensory loss (n=15). Based on CPM and temporal summation of pain (TSP), four distinct groups were formed, dysfunctional central processing group (n=27) had suboptimal CPM and present TSP, dysfunctional inhibition group (n=136) had suboptimal CPM and absent TSP, facilitation group (n=18) had optimal CPM and present TSP, and functional central processing (n=112) had optimal CPM and absent TSP. A significant association between the psychosocial and somatosensory profiles. However, no association was observed between the psychosocial or somatosensory profiles and pain modulatory profiles. CONCLUSION: Our results provide evidence that adolescents with chronic musculoskeletal pain are a heterogenous population comprising subgroups that may reflect distinct mechanisms and may benefit from different treatment approaches. The combination of screening self-reported questionnaires, QST, and CPM facilitate subgrouping of adolescents with chronic MSK pain in the clinical context and may ultimately contribute to personalized therapy.

Electroencephalographic characteristics of children and adolescents with chronic musculoskeletal pain.

Introduction: The pathophysiology of pediatric musculoskeletal (MSK) pain is unclear, contributing to persistent challenges to its management. Objectives: This study hypothesizes that children and adolescents with chronic MSK pain (CPs) will show differences in electroencephalography (EEG) features at rest and during thermal pain modalities when compared with age-matched controls. Methods: One hundred forty-two CP patients and 45 age-matched healthy controls (HCs) underwent a standardized thermal tonic heat and cold stimulations, while a 21-electrode headset collected EEG data. Cohorts were compared with respect to their EEG features of spectral power, peak frequency, permutation entropy, weight phase-lag index, directed phase-lag index, and node degree at 4 frequency bands, namely, delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz), at rest and during the thermal conditions. Results: At rest, CPs showed increased global delta (P = 0.0493) and beta (P = 0.0002) power in comparison with HCs. These findings provide further impetus for the investigation and prevention of long-lasting developmental sequalae of early life chronic pain processes. Although no cohort differences in pain intensity scores were found during the thermal pain modalities, CPs and HCs showed significant difference in changes in EEG spectral power, peak frequency, permutation entropy, and network functional connectivity at specific frequency bands (P < 0.05) during the tonic heat and cold stimulations. Conclusion: This suggests that EEG can characterize subtle differences in heat and cold pain sensitivity in CPs. The complementation of EEG and evoked pain in the clinical assessment of pediatric chronic MSK pain can better detect underlying pain mechanisms and changes in pain sensitivity.

Clinical use of Electroencephalography in the Assessment of Acute Thermal Pain: A Narrative Review Based on Articles From 2009 to 2019.

Nowadays, no practical system has successfully been able to decode and predict pain in clinical settings. The inability of some patients to verbally express their pain creates the need for a tool that could objectively assess pain in these individuals. Neuroimaging techniques combined with machine learning are seen as possible candidates for the identification of pain biomarkers. This review aimed to address the potential use of electroencephalographic features as predictors of acute experimental pain. Twenty-six studies using only thermal stimulations were identified using a PubMed and Scopus search. Combinations of the following terms were used: "EEG," "Electroencephalography," "Acute," "Pain," "Tonic," "Noxious," "Thermal," "Stimulation," "Brain," "Activity," "Cold," "Subjective," and "Perception." Results revealed that contact-heat-evoked potentials have been widely recorded over central areas during noxious heat stimulations. Furthermore, a decrease in alpha power over central regions was revealed, as well as increased theta and gamma powers over frontal areas. Gamma and theta rhythms were associated with connectivity between sensory and affective regions involved in pain processing. A machine learning analysis revealed that the gamma band is a predominant predictor of acute thermal pain. This review also addressed the need of supplementing current spectral features with techniques that allow the investigation of network dynamics.

Predicting Acute Postoperative Pain Trajectories and Long-Term Outcomes of Adolescents after Spinal Fusion Surgery.

Objectives: Acute pain trajectories are associated with long-term outcomes such as persistent pain and functional disability in adults. However, there are limited data on acute postoperative pain trajectories in the pediatric population. The aims of this study were to investigate acute postoperative pain trajectories, their predictors, and their impact on long- term outcomes in adolescents with idiopathic scoliosis. Methods: We evaluated the preoperative pain intensity, use of analgesics, psychosocial measures and physical functioning of adolescents scheduled to undergo spinal fusion, and their average 6-hour self-reported pain intensity scores for their entire hospital stay. Six months after surgery, baseline variables were reassessed. We used growth mixture modeling to conduct acute postoperative pain trajectory analysis and to identify predictors of pain trajectories. Generalized linear models were conducted to determine whether acute pain trajectories predict long-term outcomes. Results: One hundred and six patients were included in the best-fitted acute pain trajectory model that included four classes that differed in initial pain intensity and rates of change over time. Preoperative pain catastrophizer status and use of analgesics significantly predicted pain trajectory membership. Furthermore, at the 6-month follow-up, patients experiencing moderate-to-severe pain in the acute postoperative period were more likely to report higher levels of pain severity, use pain medication, and miss a greater number of school/work days due to back pain in the last three months. Discussion. Preoperative assessment and analyzing the progression of pain in the acute postoperative period can help identify those at risk of negative long-term outcomes after surgery.

Acute postoperative opioid consumption trajectories and long-term outcomes in pediatric patients after spine surgery.

Background: The days following surgery are a critical period where the use of opioids predicts long-term outcomes in adults. It is currently unknown as to whether opioid consumption throughout the acute postoperative period is associated with long-term outcomes in pediatric patients. The aims of this study were to characterize opioid consumption trajectories in the acute postoperative period, identify predictors of trajectory membership and determine associations between opioid consumption trajectories and long-term patient outcomes. Materials and methods: Medication use, pain and mental health status were assessed at baseline in adolescents with idiopathic scoliosis who were scheduled for spinal fusion surgery. Cumulative 6-hr opioid consumption was recorded for up to 5 days after spinal surgery. At 6 months after surgery, medication use, pain and functional activity were evaluated. Growth mixture modeling was used to identify opioid trajectories. Results: One hundred and six patients were included in the study. Mean cumulative 6-hr opioid consumption in the acute postoperative period was 13.23±5.20 mg/kg. The model with the best fit contained 5 acute postoperative trajectories and a quadratic term (AIC =6703.26, BIC =6767.19). Two types of patient behaviors were identified: high opioid consumers (trajectories 4 and 5) and low opioid consumers (trajectories 1, 2 and 3). Intraoperative intrathecal morphine dose was a predictor of trajectory membership (p=0.0498). Opioid consumption during the acute postoperative period was not significantly associated with pain, functional activity or pain medication use at 6 months after surgery. Conclusion: In pediatric patients, intraoperative intrathecal morphine dose predicts opioid consumption in the acute postoperative period. Importantly, opioid consumption during this period does not affect long-term outcomes in pediatric patients after a spine surgery.

Evidence of impaired pain modulation in adolescents with idiopathic scoliosis and chronic back pain.

BACKGROUND CONTEXT: Although 40% of adolescent idiopathic scoliosis (AIS) patients present with chronic back pain, the pathophysiology and underlying pain mechanisms remain poorly understood. We hypothesized that development of chronic pain syndrome in AIS is associated with alterations in pain modulatory mechanisms. PURPOSE: To identify the presence of sensitization in nociceptive pathways and to assess the efficacy of the diffuse noxious inhibitory control in patients with AIS presenting with chronic back pain. STUDY DESIGN: Cross-sectional study. PATIENT SAMPLE: Ninety-four patients diagnosed with AIS and chronic back pain. OUTCOME MEASURES: Quantitative sensory testing (QST) assessed pain modulation and self-reported questionnaires were used to assess pain burden and health-related quality of life. METHODS: Patients underwent a detailed pain assessment using a standard and validated quantitative sensory testing (QST) protocol. The measurements included mechanical detection thresholds (MDT), pain pressure threshold (PPT), heat pain threshold (HPT), heat tolerance threshold (HTT), and a conditioned pain modulation (CPM) paradigm. Altogether, these tests measured changes in regulation of the neurophysiology underlying the nociceptive processes based on the patient's pain perception. Funding was provided by The Louise and Alan Edwards Foundation and The Shriners Hospitals for Children. RESULTS: Efficient pain inhibitory response was observed in 51.1% of patients, while 21.3% and 27.7% had sub-optimal and inefficient CPM, respectively. Temporal summation of pain was observed in 11.7% of patients. Significant correlations were observed between deformity severity and pain pressure thresholds (p=.023) and CPM (p=.017), neuropathic pain scores and pain pressure thresholds (p=.015) and temporal summation of pain (p=.047), and heat temperature threshold and pain intensity (p=.048). CONCLUSIONS: Chronic back pain has an impact in the quality of life of adolescents with idiopathic scoliosis. We demonstrated a high prevalence of impaired pain modulation in this group. The association between deformity severity and somatosensory dysfunction may suggest that spinal deformity can be a trigger for abnormal neuroplastic changes in this population contributing to chronic pain syndrome.

Safety of Patient-Controlled Analgesia After Surgery in Children And Adolescents: Concerns And Potential Solutions.

Patient-controlled analgesia (PCA) is common practice for acute postoperative pain management. Postoperative PCA use decreases pain intensity and improves patient satisfaction when compared to non-PCA routes of medication administration. Although PCA has several advantages regarding efficacy and safety, adverse events remain a concern. Programming errors and protocols, patient monitoring, and PCA by proxy or with continuous infusion are recurring silent dangers of PCA use in children and adolescents. Innovative considerations need to be emphasized for future improvement of PCA devices for elective surgical patients. With technology within the healthcare setting advancing at a fast pace, smart pump technology is something to look forward to.