Phenotypic profile clustering pragmatically identifies diagnostically and mechanistically informative subgroups of chronic pain patients.

ABSTRACT: Traditional classification and prognostic approaches for chronic pain conditions focus primarily on anatomically based clinical characteristics not based on underlying biopsychosocial factors contributing to perception of clinical pain and future pain trajectories. Using a supervised clustering approach in a cohort of temporomandibular disorder cases and controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment study, we recently developed and validated a rapid algorithm (ROPA) to pragmatically classify chronic pain patients into 3 groups that differed in clinical pain report, biopsychosocial profiles, functional limitations, and comorbid conditions. The present aim was to examine the generalizability of this clustering procedure in 2 additional cohorts: a cohort of patients with chronic overlapping pain conditions (Complex Persistent Pain Conditions study) and a real-world clinical population of patients seeking treatment at duke innovative pain therapies. In each cohort, we applied a ROPA for cluster prediction, which requires only 4 input variables: pressure pain threshold and anxiety, depression, and somatization scales. In both complex persistent pain condition and duke innovative pain therapies, we distinguished 3 clusters, including one with more severe clinical characteristics and psychological distress. We observed strong concordance with observed cluster solutions, indicating the ROPA method allows for reliable subtyping of clinical populations with minimal patient burden. The ROPA clustering algorithm represents a rapid and valid stratification tool independent of anatomic diagnosis. ROPA holds promise in classifying patients based on pathophysiological mechanisms rather than structural or anatomical diagnoses. As such, this method of classifying patients will facilitate personalized pain medicine for patients with chronic pain.

Cortical processing of facial tactile stimuli in temporomandibular disorder as revealed by magnetoencephalography.

We used magnetoencephalography (MEG) to investigate the cortical processing of an innocuous facial tactile stimulus in healthy subjects and in a group of subjects suffering from chronic temporomandibular disorder (TMD). Equivalent current dipoles (ECDs) were extracted for a time period of 1 s following stimulus application, and their location, duration and onset time determined. The counts of ECDs extracted did not differ significantly between the two groups. In contrast, we found statistically significant differences in ECD duration and onset time. Specifically, ECD duration was longer in the TMD group in the precentral gyrus, and ECD onset time was earlier in the parietal operculum. In addition, we found differences in the internal organization and clustering of the brain areas involved indicating a less tight association and a less coordinated stimulus information processing in the TMD group. Altogether, these results show that an innocuous facial tactile stimulus is differently processed in the brain of TMD subjects, when compared to controls, reflecting altered brain mechanisms due to chronic pain.

Cortical processing of tactile stimuli applied in quick succession across the fingertips: temporal evolution of dipole sources revealed by magnetoencephalography.

We used magnetoencephalography (MEG) in 10 healthy human subjects to study cortical responses to tactile stimuli applied to the fingertips of digits 2-5 of the right hand. Each stimulus lasted 50 ms and was produced by air-driven elastic membranes. Four-hundred stimuli were delivered on each finger in three temporal patterns (conditions). In the "Discrete" condition, stimuli were applied to each finger repetitively with an interstimulus interval (ISI) of 1-2 s. In the "Continuous" condition, stimuli were applied to the fingers sequentially as four-stimulus trains with zero ISI and 1-2 s intervening between trains. Finally, in the "Gap" condition, stimuli were applied as in the Continuous condition but with an ISI of 50 ms. A sensation of tactile motion across fingers (digit 2 --> digit 5) was reported by all subjects in the Continuous and Gap conditions. Cortical responses were extracted as single equivalent current dipoles over a period of 1 s following stimulus onset. In all three conditions, initial responses in left primary somatosensory cortex (SI) were observed ~20 to 50 ms after stimulus onset and were followed by additional left SI responses and bilateral responses in the secondary somatosensory cortex (SII). In addition, in the Continuous and Gap conditions, there was an activation of the precentral gyrus, the temporal aspects of which depended on the temporal relation of the administered stimuli, as follows. An ISI of 0 ms led to activation of the precentral gyrus shortly after the second stimulation, whereas an ISI of 50 ms led to activation of the precentral gyrus after the third stimulation. The current findings support results from previous studies on temporal activity patterns in SI and SII, verify the participation of the precentral gyrus during tactile motion perception and, in addition, reveal aspects of integration of sequential sensory stimulations over nonadjacent areas as well as temporal activity patterns in the postcentral and precentral gyri.

Neurovascular pains: implications of migraine for the oral and maxillofacial surgeon.

Epidemiologic studies have shown that migraine headaches are a common finding in the general population, often associated with a high degree of disability. Additionally, migraine has a reported comorbidity with other medical conditions, most notably with chronic pains, such as temporomandibular disorders. The pathophysiologic mechanisms involved with migraine are suggestive of an increased and prolonged hyperexcitability to stimuli, especially within the trigeminal distribution. Because migraine is mediated by branches of the trigeminal nerve it has the potential to mimic other types of pains, such as toothache or sinusitis. It is therefore recommended that oral and maxillofacial surgeons be familiar with the diagnostic criteria for migraine headaches to identify and appropriately treat such individuals who present to their clinics.

Synchronous neural interactions assessed by magnetoencephalography: a functional biomarker for brain disorders.

We report on a test to assess the dynamic brain function at high temporal resolution using magnetoencephalography (MEG). The essence of the test is the measurement of the dynamic synchronous neural interactions, an essential aspect of the brain function. MEG signals were recorded from 248 axial gradiometers while 142 human subjects fixated a spot of light for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) and their z-transforms (z(ij)(0)) between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of z(ij)(0) successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimer's disease, schizophrenia, Sjögren's syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results.

Multifactorial assessment of measurement errors affecting intraoral quantitative sensory testing reliability.

BACKGROUND AND PURPOSE (AIMS): Measurement error of intraoral quantitative sensory testing (QST) has been assessed using traditional methods for reliability, such as intraclass correlation coefficients (ICCs). Most studies reporting QST reliability focused on assessing one source of measurement error at a time, e.g., inter- or intra-examiner (test-retest) reliabilities and employed two examiners to test inter-examiner reliability. The present study used a complex design with multiple examiners with the aim of assessing the reliability of intraoral QST taking account of multiple sources of error simultaneously. METHODS: Four examiners of varied experience assessed 12 healthy participants in two visits separated by 48h. Seven QST procedures to determine sensory thresholds were used: cold detection (CDT), warmth detection (WDT), cold pain (CPT), heat pain (HPT), mechanical detection (MDT), mechanical pain (MPT) and pressure pain (PPT). Mixed linear models were used to estimate variance components for reliability assessment; dependability coefficients were used to simulate alternative test scenarios. RESULTS: Most intraoral QST variability arose from differences between participants (8.8-30.5%), differences between visits within participant (4.6-52.8%), and error (13.3-28.3%). For QST procedures other than CDT and MDT, increasing the number of visits with a single examiner performing the procedures would lead to improved dependability (dependability coefficient ranges: single visit, four examiners=0.12-0.54; four visits, single examiner=0.27-0.68). A wide range of reliabilities for QST procedures, as measured by ICCs, was noted for inter- (0.39-0.80) and intra-examiner (0.10-0.62) variation. CONCLUSION: Reliability of sensory testing can be better assessed by measuring multiple sources of error simultaneously instead of focusing on one source at a time. In experimental settings, large numbers of participants are needed to obtain accurate estimates of treatment effects based on QST measurements. This is different from clinical use, where variation between persons (the person main effect) is not a concern because clinical measurements are done on a single person. IMPLICATIONS: Future studies assessing sensory testing reliability in both clinical and experimental settings would benefit from routinely measuring multiple sources of error. The methods and results of this study can be used by clinical researchers to improve assessment of measurement error related to intraoral sensory testing. This should lead to improved resource allocation when designing studies that use intraoral quantitative sensory testing in clinical and experimental settings.

Case series of four different headache types presenting as tooth pain.

Case reports in the literature discuss various headache disorders that present as pain in the face. The current understanding of neuroanatomy and headache mechanisms suggests that headache pain originates within intracranial structures and is then referred to the face, jaws, and teeth. This case series describes four patients, one each with migraine headache, cluster headache, paroxysmal hemicrania, and hemicrania continua, all of which who presented to dentists with the chief complaint of tooth pain. This is the first report of hemicrania continua presenting as tooth pain. It is important that dentists be cognizant of headache disorders so that they may be able to identify headache pains masquerading as toothache.

Design and Outcomes of a Comprehensive Care Experience Level System to Evaluate and Monitor Dental Students' Clinical Progress.

A Comprehensive Care Experience Level (CCEL) system that is aligned with Commission on Dental Accreditation (CODA) standards, promotes comprehensive care and prevention, and addresses flaws observed in previous Relative Value Units (RVU)-based programs has been implemented at the School of Dental Medicine, Case Western Reserve University since 2011. The purpose of this article is to report on the design, implementation, and preliminary outcomes of this novel clinical evaluation system. With the development of the CCEL concept, it was decided not to award points for procedures performed on competency exams. The reason behind this decision was that exams are not learning opportunities and are evaluated with summative tools. To determine reasonable alternative requirements, production data from previous classes were gathered and translated into CCEL points. These RVU points had been granted selectively only for restorative procedures completed after the initial preparation stage of the treatment plan, and achievement of the required levels was checked at multiple points during the clinical curriculum. Results of the CCEL system showed that low performing students increased their productivity, overall production at graduation increased significantly, and fluoride utilization to prevent caries rose by an order of magnitude over the RVU system. The CCEL program also allowed early identification and remediation of students having difficulty in the clinic. This successful implementation suggests that the CCEL concept has the potential for widespread adoption by dental schools. This method also can be used as a behavior modification tool to achieve specific patient care or clinical educational goals as illustrated by the way caries prevention was promoted through the program.

Dental Students' Learning Experiences and Preferences Regarding Orofacial Pain: A Cross-Sectional Study.

Pain is a global health problem, the effects of which range from diminished quality of life to pain management costs and loss of work and productivity. Pain in the head and neck region is defined as a separate entity: orofacial pain (OFP). However, some graduates from dental schools have reported feeling less competent in their ability to diagnose OFP than in other areas of dentistry. The aims of this study were to assess how students at one U.S. dental school had learned about OFP and to identify the teaching methods and venues they would like to see enhanced in the school's OFP curriculum. A cross-sectional four-question survey was administered to 140 dental students in their third and fourth years; the survey had a response rate of 53%. Most students reported having gained their OFP knowledge mainly in dental school, and 91.9% selected didactic courses as the main teaching method in which they had learned about this topic. Clinical education was the main teaching venue these students said they would like to see enhanced in order to gain more knowledge in most forms of OFP; this result aligned with their learning preferences in general. These findings may help dental schools design their OFP curricula to take account of students' preferences as well as practical limitations regarding availability of clinical experiences.

Dental students' perceived level of competence in orofacial pain.

Orofacial pain (OFP) is a group of symptoms affecting a significant portion of the population; inadequate diagnosis and management of these symptoms present a potential detrimental effect on the public's health. It has been suggested that dental schools must prepare their graduates to deal with these problems rather than relying on their participation in continuing education courses after graduation. The aim of this study was to determine how third- and fourth-year students at one dental school perceived their level of competence related to OFP. Out of 140 students who were sent the survey, seventy-four (53 percent response rate) completed it in its entirety. The cross-sectional survey included questions regarding the students' familiarity with the categories of OFP. Questions asked how they perceived their knowledge in each of these areas, how comfortable they felt providing diagnosis and treatment, and if more knowledge was needed. The results showed that the fourth-year students were more comfortable than the third-year students in diagnosing and managing intraoral pain. Multiple comparisons also showed statistically significant differences between OFP categories for questions related to perceived knowledge, comfort in diagnosing and treating, and perceived need for more information. Overall, the students' perceived knowledge of and confidence in treating OFP varied with respect to certain categories, being lowest for psychogenic pain.