Classification of qualitative fieldnotes collected during quantitative sensory testing: a step towards the development of a new mixed methods approach in pain rseearch

Purpose: Quantitative sensory testing (QST) is a standardized method to assess somatosensory function. The collection of qualitative information, during the QST procedure, could be an interesting way to facilitate the characterization of altered sensory perception and the identification of different pain phenotypes. The aims of this study were 1) to classify qualitative fieldnotes of sensory abnormalities collected during an independent QST study, and 2) to generate a qualitative interview guide that could be included in the traditional QST procedure as a step towards the implementation of a mixed methods approach. Patients and Methods: QST data were collected from 48 chronic neuropathic pain patients treated with spinal cord stimulation (SCS). Three body areas, with or without SCS, were tested: the painful limb targeted by SCS, the contralateral area, and the ipsilateral upper limb. After each trial of each QST modality, patients were encouraged to report any sensory abnormalities they could identify with a pain quality scale or using their own words. Results: Qualitative self-reported sensory abnormalities were dichotomized into two groups: altered sensory intensities and altered sensory perceptions. Altered sensory intensities were classified as sensory loss or sensory gain subgroups. Altered sensory perceptions were classified as paresthesia and dysesthesia subgroups Overall, 630 qualitative fieldnotes of altered sensations were collected: 385 on the painful limb, 173 at the contralateral area, and 72 at the ipsilateral upper limb. Based on these qualitative data, we propose a standardized method to collect qualitative data involving 9 open- and close-ended questions and 21 codes. Conclusion: Our findings have highlighted the value of qualitative sensory evaluation during QST and constitute an important milestone in the development of a mixed methods protocol in phenotyping research

Herpes Simplex Virus Dances with Amyloid Precursor Protein while Exiting the Cell

Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the neuronal nucleus to enter latency. Upon reawakening newly synthesized viral particles travel anterograde back to the epithelial cells of the lip, causing the recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein and receptor for anterograde transport machinery that when proteolyzed produces A-beta, the major component of senile plaques. Here we focus on transport inside epithelial cells of newly synthesized virus during its transit to the cell surface. We hypothesize that HSV1 recruits cellular APP during transport. We explore this with quantitative immuno-fluorescence, immuno-gold electron-microscopy and live cell confocal imaging. After synchronous infection most nascent VP26-GFP-labeled viral particles in the cytoplasm co-localize with APP (72.8+/−6.7%) and travel together with APP inside living cells (81.1+/−28.9%). This interaction has functional consequences: HSV1 infection decreases the average velocity of APP particles (from 1.1+/−0.2 to 0.3+/−0.1 µm/s) and results in APP mal-distribution in infected cells, while interplay with APP-particles increases the frequency (from 10% to 81% motile) and velocity (from 0.3+/−0.1 to 0.4+/−0.1 µm/s) of VP26-GFP transport. In cells infected with HSV1 lacking the viral Fc receptor, gE, an envelope glycoprotein also involved in viral axonal transport, APP-capsid interactions are preserved while the distribution and dynamics of dual-label particles differ from wild-type by both immuno-fluorescence and live imaging. Knock-down of APP with siRNA eliminates APP staining, confirming specificity. Our results indicate that most intracellular HSV1 particles undergo frequent dynamic interplay with APP in a manner that facilitates viral transport and interferes with normal APP transport and distribution. Such dynamic interactions between APP and HSV1 suggest a mechanistic basis for the observed clinical relationship between HSV1 seropositivity and risk of Alzheimer's disease

Current methodological approaches in conditioned pain modulation assessment in pediatrics

Philippe S Hwang,1 My-Linh Ma,1–3 Nora Spiegelberg,1 Catherine E Ferland1–5 1Shriners Hospital for Children – Canada, 2Research Institute – McGill University Health Centre, 3Department of Experimental Surgery, 4Department of Anesthesia, McGill University, 5The Alan Edwards Centre for Research on Pain, Montreal, QC, Canada Abstract: Conditioned pain modulation (CPM) paradigms have been used in various studies with healthy and non-healthy adult populations in an attempt to elucidate the mechanisms of pain processing. However, only a few studies so far have applied CPM in pediatric populations. Studies finding associations with chronic pain conditions suggest that deficiencies in underlying descending pain pathways may play an important role in the development and persistence of pain early in life. Twelve studies were identified using a PubMed search which examine solely pediatric populations, and these are reviewed with regard to demographics studied, methodological approaches, and conclusions reached. This review aimed to provide both clinicians and researchers with a brief overview of the current state of research regarding the use of CPM in children and adolescents, both healthy and clinical patients. The implications of CPM in experimental and clinical settings and its potential to aid in refining considerations to individualize treatment of pediatric pain syndromes will be discussed. Keywords: conditioned pain modulation, descending endogenous pain inhibition, chronic pain, pediatrics&nbsp

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

Mandy MJ Li,1,2 Don Daniel Ocay,2,3 Alisson R Teles,2,4 Pablo M Ingelmo,5,6 Jean A Ouellet,1–2,7 M Gabrielle Pagé,8,9 Catherine E Ferland2,4–6,101Faculty of Medicine, McGill University, Montreal, Quebec, Canada; 2Department of Clinical Research, Shriners Hospitals for Children-Canada, Montreal, Quebec, Canada; 3Department of Experimental Surgery, McGill University, Montreal, Quebec, Canada; 4Integrated Program in Neurosciences, McGill University, Montreal, Quebec, Canada; 5Chronic Pain Services, Montreal Children’s Hospital, Montreal, Quebec, Canada; 6Department of Anesthesia, McGill University, Montreal, Quebec, Canada; 7Division of Orthopaedic Surgery, McGill University, Montreal, Quebec, Canada; 8Département d’anesthésiologie, Université de Montréal, Montreal, Quebec, Canada; 9Carrefour de l’innovation et de l’évaluation en santé, Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, Quebec, Canada; 10Child Health and Human Development Research Axis, Research Institute-McGill University Health Centre, Montreal, Quebec, CanadaBackground: 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.Keywords: opioids, pediatrics, postsurgical pain, trajectories, adolescent idiopathic scoliosis, spinal fusion surger