Slow touch and ultrafast pain fibres: Revisiting peripheral nerve classification.

One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification. Here, we review the evidence for unmyelinated (C) fibres signalling touch at a slow conduction velocity and likely contributing to affective aspects of tactile information. We also review the evidence for large-diameter Aß afferents signalling pain at ultrafast conduction velocity and likely contributing to the rapid nociceptive withdrawal reflex. These discoveries imply that conduction velocity is not as clear-cut an indication of the functional role of the axon as previously thought. We finally suggest that a future taxonomy of the peripheral afferent nervous system might be based on the combination of the axons molecular expression and electrophysiological response properties.

Performance Evaluation of a Supervised Machine Learning Pain Classification Model Developed by Neonatal Nurses.

BACKGROUND: Early-life pain is associated with adverse neurodevelopmental consequences; and current pain assessment practices are discontinuous, inconsistent, and highly dependent on nurses' availability. Furthermore, facial expressions in commonly used pain assessment tools are not associated with brain-based evidence of pain. PURPOSE: To develop and validate a machine learning (ML) model to classify pain. METHODS: In this retrospective validation study, using a human-centered design for Embedded Machine Learning Solutions approach and the Neonatal Facial Coding System (NFCS), 6 experienced neonatal intensive care unit (NICU) nurses labeled data from randomly assigned iCOPEvid (infant Classification Of Pain Expression video) sequences of 49 neonates undergoing heel lance. NFCS is the only observational pain assessment tool associated with brain-based evidence of pain. A standard 70% training and 30% testing split of the data was used to train and test several ML models. NICU nurses' interrater reliability was evaluated, and NICU nurses' area under the receiver operating characteristic curve (AUC) was compared with the ML models' AUC. RESULTS: Nurses weighted mean interrater reliability was 68% (63%-79%) for NFCS tasks, 77.7% (74%-83%) for pain intensity, and 48.6% (15%-59%) for frame and 78.4% (64%-100%) for video pain classification, with AUC of 0.68. The best performing ML model had 97.7% precision, 98% accuracy, 98.5% recall, and AUC of 0.98. IMPLICATIONS FOR PRACTICE AND RESEARCH: The pain classification ML model AUC far exceeded that of NICU nurses for identifying neonatal pain. These findings will inform the development of a continuous, unbiased, brain-based, nurse-in-the-loop Pain Recognition Automated Monitoring System (PRAMS) for neonates and infants.

Pain-driven emergency department visits and food insecurity: a cross-sectional study linking Canadian survey and health administrative data.

BACKGROUND: As the leading cause of emergency department visits in Canada, pain disproportionately affects socioeconomically disadvantaged populations. We examine the association between household food insecurity and individuals' pain-driven emergency department visits. METHODS: We designed a cross-sectional study linking the Canadian Community Health Survey 2005-2017 to the National Ambulatory Care Reporting System 2003-2017. Food insecurity was measured using a validated questionnaire. We excluded individuals with missing food insecurity status, individuals younger than 12 years and jurisdiction-years with partial emergency department records. We assessed emergency department visits driven by pain at different sites (migraine, other headaches, chest-throat pain, abdomen-pelvis pain, dorsalgia, joint pain, limb pain, other pain) and their characteristics (frequency, cause, acuity and time of emergency department visit) in Ontario and Alberta. We adjusted for sociodemographic characteristics, lifestyle and prior non-pain-driven emergency department visits in the models. RESULTS: The sample contained 212 300 individuals aged 12 years and older. Compared with food-secure individuals, marginally, moderately and severely food-insecure people had 1.42 (95% confidence interval [CI] 1.20-1.68), 1.64 (95% CI 1.37-1.96) and 1.99 (95% CI 1.61-2.46) times higher adjusted incidence rates of pain-driven emergency department visits, respectively. The association was similar across sexes and significant among adults but not adolescents. Food insecurity was further associated with site-specific pain, with severely food-insecure individuals having significantly higher pain incidence than food-secure individuals. Severe food insecurity predicted more frequent, multicause, high-acuity and after-hours emergency department visits. INTERPRETATION: Household food insecurity status is significantly associated with pain-driven emergency department visits in the Canadian population. Policies targeting food insecurity may reduce pain and emergency department utilization.

Antinociceptive effect of N-(9,13b-dihydro-1H-dibenzo[c, f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide on different pain models in mice

Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.

Alleviation of neuropathic pain by trazodone in rats

Abstract Neuropathic pain is generally characterised by an abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia). The present study was designed to investigate the effect of trazodone (5mg/kg and 10mg/kg) on peripheral neuropathic pain induced by partial sciatic nerve ligation in rats. Mechanical hyperalgesia, cold allodynia and thermal hyperalgesia were assessed by performing the pinprick, acetone, and hot plate tests, respectively. Biochemically, lipid peroxidation level and total calcium levels were measured. However, trazodone administration (5 and 10 mg/ kg i.p.) for 21days significantly diminished partial sciatic nerve ligation-induced neuropathic pain along with areduction in oxidative stress and calcium levels. The results of the present study suggest that trazodone is effective in attenuating partial sciatic nerve ligation-inducedpainful neuropathic states, which may be attributed to decreased oxidative stress and calcium levels.

The Relationship Between Neuroprotective Activity and Antigenotoxic and Acetylcholinesterase Inhibitory Effects of Glaucium corniculatum Extracts

Abstract The purpose of this study was to investigate the relationship between the acetylcholinesterase (AChE) inhibitory and antigenotoxic effect with the neuroprotective activity of Glaucium corniculatum methanol and water extracts rich in rutin and quercetin flavonoids. Neuroprotective activity in terms of cell survival and development against oxidative damage was measured by MTT assay and microscopic analysis in H2O2-induced NGF-differentiated PC12 (dPC12) cells. QRT-PCR and western blot hybridization method was employed for the determination of AChE inhibition of the extracts in the same cell model, and the genotoxic and antigenotoxic effects were identified with Comet assay with human lymphocytes. H2O2-induced vitality loss in dPC12 cells was inhibited in pre-treated cells with these plant extracts. Moreover, extracts stimulated neurite formation and prevented the oxidative stress-induced reduction in neurite growth. In general, it was determined that G. corniculatum methanol extract containing higher amounts of rutin and quercetin was more effective than water extract in terms of AChE inhibitory, antigenotoxic and also neuroprotective effect. In this study, it was shown for the first time that both AChE inhibitory and antigenotoxic effects of G. corniculatum may be effective in neuroprotection and it's protective and therapeutic effects against neurodegeneration may be related to the flavonoid content.

Chronic pain: an update on burden, best practices, and new advances.

Chronic pain exerts an enormous personal and economic burden, affecting more than 30% of people worldwide according to some studies. Unlike acute pain, which carries survival value, chronic pain might be best considered to be a disease, with treatment (eg, to be active despite the pain) and psychological (eg, pain acceptance and optimism as goals) implications. Pain can be categorised as nociceptive (from tissue injury), neuropathic (from nerve injury), or nociplastic (from a sensitised nervous system), all of which affect work-up and treatment decisions at every level; however, in practice there is considerable overlap in the different types of pain mechanisms within and between patients, so many experts consider pain classification as a continuum. The biopsychosocial model of pain presents physical symptoms as the denouement of a dynamic interaction between biological, psychological, and social factors. Although it is widely known that pain can cause psychological distress and sleep problems, many medical practitioners do not realise that these associations are bidirectional. While predisposing factors and consequences of chronic pain are well known, the flipside is that factors promoting resilience, such as emotional support systems and good health, can promote healing and reduce pain chronification. Quality of life indicators and neuroplastic changes might also be reversible with adequate pain management. Clinical trials and guidelines typically recommend a personalised multimodal, interdisciplinary treatment approach, which might include pharmacotherapy, psychotherapy, integrative treatments, and invasive procedures.

Valoración de dolor al paciente en la unidad de terapia de adultos / Pain assessment for the patient in the adult therapy unit

La mirada histórica retrospectiva del dolor nos posiciona frente a su coexistencia con la humanidad. Cada cultura tuvo su peculiar manera de afrontarlo, darle significado y tomar sus medidas de alivio. La ciencia, desde su lugar, ha desarrollado conceptos explicando razones y orígenes de su presencia. Las ciencias médicas en su anhelo de aliviar las dolencias de las personas, elaboraron escalas de evaluación del dolor. En las terapias intensivas, donde el estado de conciencia del paciente varía acorde a la necesidad que se produce a fin de resolver su patología o el motivo de ingreso a este servicio, resulta necesario valorar su estado neurológico para poder así determinar con precisión la escala de evaluación del dolor que aporte el resultado más oportuna según el momento preciso. Debido a los cuidados que lleva a cabo el profesional de enfermería con los internados, es quien permanece mayor tiempo con ellos; pudiendo cultivar una relación interpersonal más profunda, y debido a lo cual, no sólo colaborar en el alivio del dolor, sino también, si fuera necesario, ayudar a que encuentre el sentido a éste, en palabras de Travelbee. Para poder implementar dicha idea, el objetivo del presente protocolo, se define el siguiente objetivo: «Tomar acuerdo e implementar el uso adecuado y continuo de las escalas del dolor, en el paciente de terapia intensiva de adultos, de acuerdo a su grado de conciencia, a fin de reducir el dolor durante su estadía de internación[AU]

The retrospective historical view of pain positions us in front of its coexistence with humanity. Each culture had its own way of dealing with it, giving it meaning, and taking its relief measures. Science, from its place, has developed concepts explaining reasons and origins of its presence. The medical sciences in their desire to alleviate people's ailments, developed pain assessment scales. In intensive therapies, where the patient's state of consciousness varies according to the need that occurs in order to resolve their pathology or the reason for admission to this service, it is necessary to assess their neurological status in order to accurately determine the scale of pain assessment that provides the most timely result according to the precise moment. Due to the care carried out by the nursing professional with the internees, it is he who stays with them the longest; being able to cultivate a deeper interpersonal relationship, and due to which, not only collaborate in the relief of pain, but also, if necessary, help it find meaning to it, in the words of Travelbee. In order to implement this idea, the objective of this protocol, the following objective is defined: "Agree and implement the adequate and continuous use of pain scales, in the adult intensive care patient[AU]

A visão histórica retrospectiva da dor nos posiciona diante de sua convivência com a humanidade. Cada cultura tinha sua própria maneira de lidar com isso, dando-lhe sentido e tomando suas medidas de alívio. A ciência, a partir de seu lugar, desenvolveu conceitos que explicam as razões e as origens de sua presença. As ciências médicas, em seu desejo de aliviar as doenças das pessoas, desenvolveram escalas de avaliação da dor. Nas terapias intensivas, onde o estado de consciência do paciente varia de acordo com a necessidade que ocorre para a resolução de sua patologia ou o motivo da admissão neste serviço, é necessário avaliar seu estado neurológico para determinar com precisão a escala de avaliação da dor que fornece o resultado mais oportuno de acordo com o momento preciso. Devido aos cuidados realizados pelo profissional de enfermagem com os internos, é ele quem fica com eles por mais tempo; ser capaz de cultivar um relacionamento interpessoal mais profundo, e por isso, não só colaborar no alívio da dor, mas também, se necessário, ajudá-la a encontrar sentido para ela, nas palavras de Travelbee. Para concretizar essa ideia, objetivo deste protocolo, é definido o seguinte objetivo: "Acordar e implementar o uso adequado e contínuo de escalas de dor, no paciente adulto em terapia intensiva, de acordo com seu grau de consciência, a fim de reduzir dor durante a sua internação[AU]

Procedural Coding for Interventional Pain Management.

Interventional radiologists' involvement in pain service lines continues to increase. While clinical and technical acumen is an obvious prerequisite, understanding the coding related to these procedures is also a must. The pain specialist's practice is largely outpatient based, therefore, the coding and subsequent billing for outpatient clinic visits may be an important revenue generator. A brief review of the evaluation and management (E&M) coding, as well as review of procedural CPT coding for pain interventions is discussed herein. While not overly difficult, there are certain nuances regarding the coding and reporting of these procedures. Developing an understanding of the proper use of CPT coding involved in pain procedures will allow the interventionalist to accurately capture the work performed and further support a pain service line. Case examples are used to reinforce certain points.

Classification of Whole-Body Postural Discomfort Using Cluster Analysis.

The objectives of this study were to evaluate the effect of gender and postures of the neck, trunk, and knee on overall postural discomfort, and to classify combined postures into different postural discomfort groups. A total of 95 participants (42 males and 53 females) performed 45 different static postures, which were a combination of 3 neck angles, 5 trunk angles, and 3 knee angles, and rated the perceived postural discomfort. Non-hierarchical K-means cluster analysis was employed to classify the 45 different combined postures into several postural discomfort groups. Postural discomfort was significantly affected by gender and postures of the neck, trunk, and knee (p < 0.001). Three clusters (high, medium, and low discomfort) were identified and the postural discomfort was significantly different between clusters (p < 0.001). The high discomfort group consisted of mostly males with high knee and trunk flexion angles and a moderate neck flexion angle. The low discomfort group was female-dominant with low neck and trunk flexion angles and a moderate knee flexion angle. The different flexibility (stiffness) of the joint motions between genders may affect the gender difference in postural discomfort. The knee and trunk postures were critical to the postural balance, which may affect the perception of whole-body discomfort. This result will be useful for developing and improving postural observation tools.

Pain phenotypes classified by machine learning using electroencephalography features.

Pain is a multidimensional experience mediated by distributed neural networks in the brain. To study this phenomenon, EEGs were collected from 20 subjects with chronic lumbar radiculopathy, 20 age and gender matched healthy subjects, and 17 subjects with chronic lumbar pain scheduled to receive an implanted spinal cord stimulator. Analysis of power spectral density, coherence, and phase-amplitude coupling using conventional statistics showed that there were no significant differences between the radiculopathy and control groups after correcting for multiple comparisons. However, analysis of transient spectral events showed that there were differences between these two groups in terms of the number, power, and frequency-span of events in a low gamma band. Finally, we trained a binary support vector machine to classify radiculopathy versus healthy subjects, as well as a 3-way classifier for subjects in the 3 groups. Both classifiers performed significantly better than chance, indicating that EEG features contain relevant information pertaining to sensory states, and may be used to help distinguish between pain states when other clinical signs are inconclusive.

[Basic Knowledge of Drug Pain Therapy in the Palliative Situation]. / Basiswissen zur medikamentösen Schmerztherapie in der Palliativsituation.

This review provides an overview of the basic knowledge of drug pain therapy in the palliative situation. Pain is one of the main symptoms in 60 to 90 % of cancer patients. Pain also develops with neurological and other diseases that occur in end-of-life situations. To address this symptom, a holistic strategy is required that encompasses all physical, psychological, social, and spiritual aspects of the multi-dimensional pain experience ("total pain" concept).Drug treatment for cancer pain has been based on a stepwise approach for many years, starting with non-opioid analgesics, followed by moderate and strong opioids. In contrast, today's pain management is determined more by the actual intensity of this aversive event.The pain assessment should be tailored to identify a nociceptive vs. neuropathic pain component that needs to be challenged by the most appropriate drug therapies. Non-opioid analgesics are ideal substances for relieving nociceptive pain. Antidepressants and anticonvulsants reduce the intensity of new neuropathic pain. Opioids are suitable for all types of pain, but are restricted to a second line choice. Among all opioids are tilidine and tramadol prodrugs, which only relieve pain after activation in the liver. Drug-drug interactions may also block this activation. Rapid release opioids should be used for cancer breakthrough pain. Transdermal opioid applications are recommended for swallowing disorders, but usually not to initiate pain control. An opioid switch can be performed if side effects such as hallucinations for the selected opioid are more pronounced than the pain reduction.

Isokinetic back training is more effective than core stabilization training on pain intensity and sports performances in football players with chronic low back pain: A randomized controlled trial.

BACKGROUND: Isokinetic training (IKT) and core stabilization training (CST) are commonly used for balance training in musculoskeletal conditions. The knowledge about the effective implementation of these training protocols on sports performances in university football players with chronic low back pain (LBP) is lacking. OBJECTIVE: To find and compare the effects of IKT and CST on sports performances in university football players with chronic LBP. DESIGN: Randomized, double-blinded controlled study. SETTING: University hospital. PARTICIPANTS: Sixty LBP participants divided into isokinetic group (IKT; n = 20), core stabilization group (CST; n = 20), and the control group (n = 20) and received respected exercises for 4 weeks. OUTCOME MEASURES: Clinical (pain intensity and player wellness) and sports performances (40 m sprint, 4 × 5 m sprint, submaximal shuttle running, counter movement jump, and squat jump) scores were measured at baseline, after 4 weeks, 8 weeks, and 3 months. RESULTS: Four weeks following training IKT group shows more significant changes in pain intensity and player wellness scores than CST and control groups (P ≤ .001). Sports performance variables (40 m sprint, 4 × 5 m sprint, submaximal shuttle running, counter movement jump and squat jump) scores also show significant improvement in IKT group than the other 2 groups (P ≤ .001). CONCLUSION: This study suggests that training through IKT improves pain intensity and sports performances than CST in university football players with chronic LBP.

African American Young Adults' Pain and Pain Reduction Strategies.

BACKGROUND: Effective acute pain management strategies are important for young adults in order to reduce risk for transition to chronic pain. AIM: To describe pain and pain self-management strategies used by African American young adults. DESIGN & SETTING: A national online cross-sectional survey design was used. PARTICIPANT/SUBJECTS: Ninety-four African Americans Qualtrics panelists ages 18-25 who reported previous experience with acute pain responded. Methods: Respondents completed the Brief Pain Inventory Short Form to describe their pain intensity, pain interference with function, pain self-management, and percent of relief obtained from their self-management. RESULTS: African American young adults reported pain primarily in the back (n = 22, 23.4%) and head (n = 19, 20.2%), with moderate pain intensity M = 4.5 (standard deviation [SD] = 1.79) and pain interference with function M = 4.6 (SD = 2.36). African American young adults described their worst pain in the last 24 hours as M = 5.7 (SD = 2.01), least pain as M = 3.4 (SD = 2.41), and average pain as M = 5.1 (SD = 2.09). They reported 61.3% pain relief from self-treatment. A total of 45 (47.9%) reported no pain self-management strategies. CONCLUSIONS: African American young adults report moderate levels of pain intensity and pain interference with function. A significant number report no pain self-management strategies. Focused pain assessment and education about efficacious pain self-management strategies, both pharmacological and complementary, could assist young African Americans to reduce their pain and risk of chronic pain in the future.

Classification of Pain Event Related Potential for Evaluation of Pain Perception Induced by Electrical Stimulation.

Variability in individual pain sensitivity is a major problem in pain assessment. There have been studies reported using pain-event related potential (pain-ERP) for evaluating pain perception. However, none of them has achieved high accuracy in estimating multiple pain perception levels. A major reason lies in the lack of investigation of feature extraction. The goal of this study is to assess four different pain perception levels through classification of pain-ERP, elicited by transcutaneous electrical stimulation on healthy subjects. Nonlinear methods: Higuchi's fractal dimension, Grassberger-Procaccia correlation dimension, with auto-correlation, and moving variance functions were introduced into the feature extraction. Fisher score was used to select the most discriminative channels and features. As a result, the correlation dimension with a moving variance without channel selection achieved the best accuracies of 100% for both the two-level and the three-level classification but degraded to 75% for the four-level classification. The best combined feature group is the variance-based one, which achieved accuracy of 87.5% and 100% for the four-level and three-level classification, respectively. Moreover, the features extracted from less than 20 trials could not achieve sensible accuracy, which makes it difficult for an instantaneous pain perception levels evaluation. These results show strong evidence on the possibility of objective pain assessment using nonlinear feature-based classification of pain-ERP.

What Do Adult Surgical Patients Speaking Primarily Cantonese, Italian, or Portuguese Really Want to Know About Pain and Pain Management?

BACKGROUND: Surgical patients consider information about pain and pain management to be highly important (Apfelbaum, 2003). At the same time, evidence indicates that members of racial and ethnic minorities are more likely to experience inadequate pain management (Green, Anderson, Baker, Campbell, Decker, Fillingim, & Todd, 2003; Mossey, 2011). AIMS: This study investigated the needs of general day surgery patients who spoke primarily Cantonese, Italian, or Portuguese at home for information about postoperative pain. DESIGN: This was a mixed methods, descriptive study. SETTING: The day surgery unit of a large, quaternary care hospital in downtown Toronto. PARTIPANTS/SUBJECTS: Inclusion criteria were day patients who were at least 18 years of age or older and spoke primariy Cantonese, Italian or Portugues at home. and were able to read and write in their primary language. METHODS: Participants who had undergone a day surgery procedure completed a telephone information needs survey in their primary language (Cantonese, Italian, Portuguese) within 72 hours after discharge. Composite mean scores were calculated for each item. Chi-squared analyses were used to probe for intergroup differences and compare with English-fluent participants from phase 1 of this study (Kastanias, Denny, Robinson, Sabo, & Snaith, 2009). RESULTS: Sixty-three participants in total completed the survey: 21% Cantonese, 41% Italian, and 38% Portuguese. The mean age of the sample was 70 years old; 89% were born outside of Canada, and 52% were male. For the combined group, the average importance rating score range for the information items was 6.2-8.9 out of a possible score of 10. All items were rated as moderate (5-6 out of 10) to high (≥7out of 10) importance. Surgical subtype, health status, and age had no effect on the importance of any information item. There were no significant differences between the three language groups on any of the information items. This lack of difference may have been a result of a lack of power due to the small sample size of the individual language groupings. Overall, the top-ranked information items were "the plan for which drugs to take and when," "what I can do if I still have pain or side effects," and "side effects I was most likely to get." CONCLUSIONS: Similar to English-fluent participants (Kastanias et al., 2009), participants who primarily spoke either Cantonese, Italian, or Portuguese at home placed moderate to high importance on all of the information items. and neither surgical subtype, health status nor age had any effect on the importance of any item. The multilingual sample in this study placed more importance than English-fluent participants on information regarding help with paying for pain medication (p = .001) and the side effects they were most likely to experience (p < .05). Due to a paucity of literature in this area, further research is warranted. Results may assist with evaluating and improving current approaches to surgical patient pain management education.

Initial classification of low back and leg pain based on objective functional testing: a pilot study of machine learning applied to diagnostics.

OBJECTIVE: The five-repetition sit-to-stand (5R-STS) test was designed to capture objective functional impairment and thus provided an adjunctive dimension in patient assessment. The clinical interpretability and confounders of the 5R-STS remain poorly understood. In clinical use, it became apparent that 5R-STS performance may differ between patients with lumbar disk herniation (LDH), lumbar spinal stenosis (LSS) with or without low-grade spondylolisthesis, and chronic low back pain (CLBP). We seek to evaluate the extent of diagnostic information contained within 5R-STS testing. METHODS: Patients were classified into gold standard diagnostic categories based on history, physical examination, and imaging. Crude and adjusted comparisons of 5R-STS performance were carried out among the three diagnostic categories. Subsequently, a machine learning algorithm was trained to classify patients into the three categories using only 5R-STS test time and patient age, gender, height, and weight. RESULTS: From two prospective studies, 262 patients were included. Significant differences in crude and adjusted test times were observed among the three diagnostic categories. At internal validation, classification accuracy was 96.2% (95% CI 87.099.5%). Classification sensitivity was 95.7%, 100%, and 100% for LDH, LSS, and CLBP, respectively. Similarly, classification specificity was 100%, 95.7%, and 100% for the three diagnostic categories. CONCLUSION: 5R-STS performance differs according to the etiology of back and leg pain, even after adjustment for demographic covariates. In combination with machine learning algorithms, OFI can be used to infer the etiology of spinal back and leg pain with accuracy comparable to other diagnostic tests used in clinical examination. These slides can be retrieved under Electronic Supplementary Material.

"Dr. Google, I am in Pain"-Global Internet Searches Associated with Pain: A Retrospective Analysis of Google Trends Data.

We aimed to rank the most common locations of pain among Google users globally and locally and analyze secular and seasonal trends in pain-related searches in the years 2004-2019. We used data generated by Google Trends (GT) to identify and analyze global interest in topics (n = 24) related to locations of pain and how these progressed over time. We analyzed secular trends and time series decomposition to identify seasonal variations. We also calculated the interest in all topics with reference to the relative search volume (RSV) of "Abdominal pain". Google users were most commonly interested in "Headache" (1.30 [times more frequently than "Abdominal pain"]), "Abdominal pain" (1.00), and "Back pain" (0.84). "Headache" was the most frequent search term in n = 41 countries, while "Abdominal pain" was the most frequent term in n = 27 countries. The interest in all pain-related topics except "Dyspareunia" increased over time. The sharpest increase was observed for "Abdominal pain" (5.67 RSV/year), and "Toothache" (5.52 RSV/year). Most of the topics revealed seasonal variations. Among pain-related topics, "Headache," "Abdominal pain," and "Back pain" interested most Google users. GT is a novel tool that allows retrospective investigation of complaints among Internet users.