The Impact of Sleep Disturbances on Endogenous Pain Modulation: A Systematic Review and Meta-Analysis.

The bidirectional relationship between sleep and pain problems has been extensively demonstrated but despite all the accumulating evidence, their shared mechanisms are currently not fully understood. This review examined the association between sleep disturbances, defined as a broad array of sleep-related outcomes (eg, poor quality, short duration, insomnia), and endogenous pain modulation (EPM) in healthy and clinical populations. Our search yielded 6,151 references, and 37 studies met the eligibility criteria. Qualitative results showed mixed findings regarding the association between sleep disturbances and temporal summation of pain (TSP) and conditioned pain modulation (CPM), with poor sleep more commonly associated with decreased pain inhibition in both populations. Quantitative results indicated that such associations were not statistically significant, neither in healthy populations when EPM outcomes were assessed for changes pre-/post-sleep intervention (TSP: .31 [95%CI: -.30 to .92]; P = .321; CPM: .40 [95%CI: -.06 to .85] P = .088) nor in clinical populations when such association was assessed via correlation (TSP: -.00 [95%CI: -.22 to .21] P = .970; CPM: .12 [95%CI: -.05 to .29]; P = .181). For studies that reported results by sex, meta-analysis showed that experimental sleep disturbances impaired pain inhibition in females (1.43 [95%CI: .98-1.88]; P < .001) but not in males (-.30 [95%CI: -2.69 to 1.60]; P = .760). Only one study investigating the association between sleep disturbances and offset analgesia was identified, while no studies assessing spatial summation of pain were found. Overall, this review provides a comprehensive overview of the association between sleep disturbances and EPM function, emphasizing the need for further investigation to clarify specific mechanisms and phenotypic subtypes. PERSPECTIVE: This review shines a light on the association between sleep disturbances and endogenous pain modulation function. Qualitatively, we found a frequent association between reduced sleep quality and impaired pain inhibition. However, quantitatively such an association was not corroborated. Sex-specific effects were observed, with females presenting sleep-related impaired pain inhibition but not males.

Differences in temporal profile of brain responses by pleasantness of somatosensory stimulation in autistic individuals.

Purpose/Aim. Autistic individuals may show either hyper- or hypo- responsiveness to touch compared to non-autistic individuals. These behavioural responses depend on perceptual and evaluative mechanisms, which unfold sequentially and thus can be distinguished by exploring the timing of neural responses. In this study, we examined neural response timing to pleasant, unpleasant, and affectively neutral textures, to determine whether these perceptual versus evaluative subprocesses differ in autism and how each subprocess contributes to behavioural responses.Materials and Methods. Our sample included n = 13 autistic and n = 14 non-autistic adults who completed functional magnetic resonance imaging. We analysed early, intermediate, and late phases of the tactile response, derived from studies of noxious tactile stimulation, to three different textures.Results. The autistic group showed distinct differences from the non-autistic group to each of the textures, showing earlier, somatosensory differences in response to the pleasantly and unpleasantly rated textures and later, frontomotor differences in response to the neutrally rated texture. Further, reduced early phase response to the pleasant texture correlated with increased sensory seeking behaviour.Conclusions. While preliminary, these results suggest distinct patterns between autistic and non-autistic individuals in how the neural response to touch unfolds and its correspondence with the perceived pleasantness of tactile experience. The findings suggest perceptual differences in response to affectively charged textures and evaluative differences in response to neutral, ambiguous textures. These temporal properties may inform future studies of tactile processing in autism, lending a better understanding of how individuals differ in their sensory experiences across contexts.

The prevalence of persistent post-traumatic headache in adult civilian traumatic brain injury: a systematic review and meta-analysis on the past 14 years.

ABSTRACT: The most recent prevalence estimate of post-traumatic headache (PTH) after traumatic brain injury (TBI) in veterans and civilians dates back to 2008. The prevalence was found to be 57.8%, with surprising higher rates (75.3%) in mild TBI when compared with those with moderate/severe TBI (32.1%). However, the revision of mild TBI diagnostic criteria and an historic peak of TBI in the elderly individuals attributed to the ageing population may lead to different results. Thus, we conducted a systematic review and meta-analysis to assess the updated prevalence of PTH during the past 14 years only in civilians. A literature search was conducted following PRISMA guidelines guided by a librarian. Screening, full-text assessment, data extraction, and risk of bias assessment were performed blindly by 2 raters. Meta-analysis of proportions using the Freeman and Tukey double arcsine method of transformation was conducted. Heterogeneity, sensitivity analysis, and meta-regressions were performed with the predictors: year of publication, mean age, sex, TBI severity, and study design. Sixteen studies were selected for the qualitative analysis and 10 for the meta-analysis. The overall prevalence estimate of PTH was 47.1%, (confidence interval = 34.6, 59.8, prediction intervals = 10.8, 85.4), being similar at different time points (3, 6, 12, and 36+ months). Heterogeneity was high, and none of the meta-regressions were significant. The overall prevalence of PTH after TBI over the past 14 years remains high even if assessed only in civilians. However, the prevalence rates attributed to mild and moderate/severe TBI were similar, differing significantly from previous reports. Efforts are needed to improve TBI outcomes.

Altered brain responses to noxious dentoalveolar stimuli in high-impact temporomandibular disorder pain patients.

High-impact temporomandibular disorder (TMD) pain may involve brain mechanisms related to maladaptive central pain modulation. We investigated brain responses to stimulation of trigeminal sites not typically associated with TMD pain by applying noxious dentoalveolar pressure to high- and low-impact TMD pain cases and pain-free controls during functional magnetic resonance imaging (fMRI). Fifty female participants were recruited and assigned to one of three groups based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and Graded Chronic Pain Scale: controls (n = 17), low-impact (n = 17) and high-impact TMD (n = 16). Multimodal whole-brain MRI was acquired following the Human Connectome Project Lifespan protocol, including stimulus-evoked fMRI scans during which painful dentoalveolar pressure was applied to the buccal gingiva of participants. Group analyses were performed using non-parametric permutation tests for parcellated cortical and subcortical neuroimaging data. There were no significant between-group differences for brain activations/deactivations evoked by the noxious dentoalveolar pressure. For individual group mean activations/deactivations, a gradient in the number of parcels surviving thresholding was found according to the TMD pain grade, with the highest number seen in the high-impact group. Among the brain regions activated in chronic TMD pain groups were those previously implicated in sensory-discriminative and motivational-affective pain processing. These results suggest that dentoalveolar pressure pain evokes abnormal brain responses to sensory processing of noxious stimuli in high-impact TMD pain participants, which supports the presence of maladaptive brain plasticity in chronic TMD pain.

Temporomandibular disorders cases with high-impact pain are more likely to experience short-term pain fluctuations.

Temporomandibular disorders (TMD) patients can present clinically significant jaw pain fluctuations which can be debilitating and lead to poor global health. The Graded Chronic Pain Scale evaluates pain-related disability and its dichotomous grading (high/low impact pain) can determine patient care pathways and in general high-impact pain patients have worse treatment outcomes. Individuals with low-impact TMD pain are thought to have better psychosocial functioning, more favorable disease course, and better ability to control pain, while individuals with high-impact pain can present with higher levels of physical and psychological symptoms. Thereby, there is reason to believe that individuals with low- and high-impact TMD pain could experience different pain trajectories over time. Our primary objective was to determine if short-term jaw pain fluctuations serve as a clinical marker for the impact status of TMD pain. To this end, we estimated the association between high/low impact pain status and jaw pain fluctuations over three visits (≤ 21-day-period) in 30 TMD cases. Secondarily, we measured the association between jaw pain intensity and pressure pain thresholds (PPT) over the face and hand, the latter measurements compared to matched pain-free controls (n = 17). Jaw pain fluctuations were more frequent among high-impact pain cases (n = 15) than low-impact pain cases (n = 15) (OR 5.5; 95% CI 1.2, 26.4; p value = 0.033). Jaw pain ratings were not associated with PPT ratings (p value > 0.220), suggesting different mechanisms for clinical versus experimental pain. Results from this proof-of-concept study suggest that targeted treatments to reduce short-term pain fluctuations in high-impact TMD pain is a potential strategy to achieve improved patient perception of clinical pain management outcomes.

Persistent dentoalveolar pain disorder: A putative intraoral chronic overlapping pain condition.

Chronic overlapping pain conditions (COPCs) are conditions that share several clinical characteristics and symptomatology, are usually considered idiopathic in nature, and are frequently comorbid. Currently, there are no established inclusion criteria to determine which conditions should be included under this umbrella term despite different systems proposed. Persistent dentoalveolar pain disorder (PDAP), also referred to as atypical odontalgia and thought to be a component of persistent idiopathic facial pain, is a chronic pain condition that manifests as a persistent tooth pain or pain over a dentoalveolar site formerly occupied by a tooth in the absence of detectable pathology during clinical or radiological examination. PDAP is considered idiopathic in nature, and its pathophysiological mechanisms are not fully understood. Our objective was to investigate whether PDAP fits the conceptual paradigm of COPC given its characteristics and commonalities with other COPC, based on published literature identified through a scoping review. We found that PDAP fits 16 out of 18 common characteristics among COPCs, and based on this finding, we discuss the implications of PDAP being considered a COPC.

Endogenous pain modulation in chronic temporomandibular disorders: Derivation of pain modulation profiles and assessment of its relationship with clinical characteristics.

BACKGROUND: Endogenous pain modulation (EPM) reflects the brain's ability to modulate incoming nociceptive inputs, and deficient EPM was implicated as a chronic pain mechanism. EPM status has been investigated in temporomandibular disorders (TMD) patients with conflicting results, and its relationship with clinical characteristics in this population is not well known. OBJECTIVES: (a) Determine EPM responses in chronic TMD cases and pain-free controls; (b) Derive pain modulation profiles (PMP) based on individual EPM responses; and (c) Categorise clinical characteristics of TMD cases and pain-free controls based on their individual PMP. METHODS: Twenty-two chronic TMD cases and 17 age-matched pain-free controls, all females, were comprehensively characterised regarding clinical characteristics and underwent EPM testing using temporal summation of pain (TSP) and conditioned pain modulation (CPM) protocols over the face and hand. Individuals were categorised into PMPs (I-IV) based on predetermined cut-off points for TSP and CPM responses. RESULTS: Between-group comparisons showed similar TSP and CPM responses (P > 0.23) in the face, while TMD cases showed significantly increased TSP (P = 0.04) but similar CPM responses (P > 0.17) in the hand relative to controls. Similar distribution across PMPs and clinical characteristics when categorised into PMPs was found for both groups. Body mass index was associated with increased TSP and reduced CPM in the face in TMD cases. CONCLUSION: Endogenous pain modulation responses over the face were similar between groups. TMD cases showed increased hand TSP compared to controls while both groups showed no significant hand CPM. PMP classification showed similar results between groups, and further refinement of PMP determination is warranted.

Endogenous pain modulation in chronic orofacial pain: a systematic review and meta-analysis.

Abnormal endogenous pain modulation was suggested as a potential mechanism for chronic pain, ie, increased pain facilitation and/or impaired pain inhibition underlying symptoms manifestation. Endogenous pain modulation function can be tested using psychophysical methods such as temporal summation of pain (TSP) and conditioned pain modulation (CPM), which assess pain facilitation and inhibition, respectively. Several studies have investigated endogenous pain modulation function in patients with nonparoxysmal orofacial pain (OFP) and reported mixed results. This study aimed to provide, through a qualitative and quantitative synthesis of the available literature, overall estimates for TSP/CPM responses in patients with OFP relative to controls. MEDLINE, Embase, and the Cochrane databases were searched, and references were screened independently by 2 raters. Twenty-six studies were included for qualitative review, and 22 studies were included for meta-analysis. Traditional meta-analysis and robust variance estimation were used to synthesize overall estimates for standardized mean difference. The overall standardized estimate for TSP was 0.30 (95% confidence interval: 0.11-0.49; P = 0.002), with moderate between-study heterogeneity (Q [df = 17] = 41.8, P = 0.001; I = 70.2%). Conditioned pain modulation's estimated overall effect size was large but above the significance threshold (estimate = 1.36; 95% confidence interval: -0.09 to 2.81; P = 0.066), with very large heterogeneity (Q [df = 8] = 108.3, P < 0.001; I = 98.0%). Sensitivity analyses did not affect the overall estimate for TSP; for CPM, the overall estimate became significant if specific random-effect models were used or if the most influential study was removed. Publication bias was not present for TSP studies, whereas it substantially influenced CPM's overall estimate. These results suggest increased pain facilitation and trend for pain inhibition impairment in patients with nonparoxysmal OFP.

Initially intact neural responses to pain in autism are diminished during sustained pain.

Pain assessments typically depend on self-report of the pain experience. Yet, in individuals with autism spectrum disorders, this can be an unreliable due to communication difficulties. Importantly, observations of behavioral hypo- and hyperresponsivity to pain suggest altered pain sensitivity in autism spectrum disorder. Neuroimaging may provide insight into mechanisms underlying pain behaviors. The neural pain signature reliably responds to painful stimulation and is modulated by other outside regions, affecting the pain experience. In this first functional magnetic resonance imaging study of pain in autism spectrum disorder, we investigated neural responses to pain in 15 adults with autism spectrum disorder relative to a typical comparison group (n = 16). We explored temporal and spatial properties of the neural pain signature and its modulators during sustained heat pain. The two groups had indistinguishable pain ratings and neural pain signature responses during acute pain; yet, we observed strikingly reduced neural pain signature response in autism spectrum disorder during sustained pain and after stimulus offset. The posterior cingulate cortex, a neural pain signature modulating region, mirrored this late signal reduction in autism spectrum disorder. Intact early responses, followed by diminished late responses to sustained pain, may reflect altered pain coping or evaluation in autism spectrum disorder. Evidence of a dichotomous neural response to initial versus protracted pain may clarify the coexistence of both hypo- and hyperresponsiveness to pain in autism spectrum disorder.

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.

Initial accuracy assessment of the modified S-LANSS for the detection of neuropathic orofacial pain conditions.

OBJECTIVE: To evaluate the accuracy of a questionnaire modified for the identification of intraoral pain with neuropathic characteristics in a clinical orofacial pain sample population. METHOD AND MATERIALS: 136 participants with at least one of four orofacial pain diagnoses (temporomandibular disorders [TMD, n = 41], acute dental pain [ADP, n = 41], trigeminal neuralgia [TN, n = 19], persistent dentoalveolar pain disorder [PDAP, n = 14]) and a group of pain-free controls (n = 21) completed the modified S-LANSS, a previously adapted version of the original questionnaire devised to detected patients suffering from intraoral pain with neuropathic characteristics. Psychometric properties (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) were calculated in two analyses with two different thresholds: (1) Detection of pain with neuropathic characteristics: PDAP + TN were considered positive, and TMD + ADP + controls were considered negative per gold standard (expert opinion). (2) Detection of PDAP: PDAP was considered positive and TMD + ADP were considered negative per gold standard. For both analyses, target values for adequate sensitivity and specificity were defined as ≥ 80%. RESULTS: For detection of orofacial pain with neuropathic characteristics (PDAP + TN), the modified S-LANSS presented with the most optimistic threshold sensitivity of 52% (95% confidence interval [CI], 34-69), specificity of 70% (95% CI, 60-79), PPV of 35% (95% CI, 22-51), and NPV of 82% (95% CI, 72-89). For detection of PDAP only, with the most optimistic threshold sensitivity was 64% (95% CI, 35-87), specificity 63% (95% CI, 52-74), PPV 23% (95% CI, 11-39) and NPV 91% (95% CI, 81-97). CONCLUSION: Based on a priori defined criteria, the modified S-LANSS did not show adequate accuracy to detect intraoral pain with neuropathic characteristics in a clinical orofacial pain sample.

Amplified Brain Processing of Dentoalveolar Pressure Stimulus in Persistent Dentoalveolar Pain Disorder Patients.

AIMS: (1) To determine the brain regions activated by dentoalveolar pressure stimulation in persistent dentoalveolar pain disorder (PDAP) patients, and (2) to compare these activation patterns to those seen in pain-free control subjects. METHODS: A total of 13 PDAP patients and 13 matched controls completed the study. Clinical pain characteristics and psychosocial data were collected. Dentoalveolar mechanical pain thresholds were determined with a custom-made device over the painful area for patients and were used as the stimulation level during functional magnetic resonance imaging (fMRI) data acquisition. Control subjects received two stimulation levels over matched locations during fMRI scanning: one determined (as above) that evoked equally subjective pain ratings matching those of patients (subjective-pain match) and another nonpainful stimulation level matching the average stimulus intensity provided to patients (stimulus-intensity match). Clinical and psychosocial data were analyzed using independent samples t tests, Mann-Whitney U test, and Spearman rank-order correlation coefficient. fMRI data were analyzed using validated neuroimaging software and tested using a general linear model. RESULTS: PDAP patients had greater anxiety (P<.0001) and depression scores (P=.001), more jaw function impairment (P<.0001), and greater social impact (P<.0001) than controls. No significant differences were found for brain activation spatial extent (PDAP X Controls subjective pain: P=.48; PDAP X Controls stimulus intensity: P=.12). Brain activations were significantly increased for PDAP patients compared to control subjects when matched to stimulus intensity in several regions related to the sensory-discriminative and cognitive components of pain perception, including the primary and secondary somatosensory cortices, inferior parietal lobule, insula, premotor cortex, prefrontal cortex, and thalamus. When matched to subjective pain ratings, increased brain activations were still present for PDAP patients compared to controls, although to a lesser extent. CONCLUSION: The present results suggest that dentoalveolar pressure is processed differently in the brain of PDAP patients, and the increased activation in several brain areas is consistent with amplified pain processing.

Perceptual and neural response to affective tactile texture stimulation in adults with autism spectrum disorders.

Autism spectrum disorders (ASD) are associated with differences in sensory sensitivity and affective response to sensory stimuli, the neural basis of which is still largely unknown. We used psychophysics and functional magnetic resonance imaging (fMRI) to investigate responses to somatosensory stimulation with three textured surfaces that spanned a range of roughness and pleasantness in a sample of adults with ASD and a control group. While psychophysical ratings of roughness and pleasantness were largely similar across the two groups, the ASD group gave pleasant and unpleasant textures more extreme average ratings than did controls. In addition, their ratings for a neutral texture were more variable than controls, indicating they are less consistent in evaluating a stimulus that is affectively ambiguous. Changes in brain blood oxygenation level-dependent (BOLD) signal in response to stimulation with these textures differed substantially between the groups, with the ASD group exhibiting diminished responses compared to the control group, particularly for pleasant and neutral textures. For the most unpleasant texture, the ASD group exhibited greater BOLD response than controls in affective somatosensory processing areas such as the posterior cingulate cortex and the insula. The amplitude of response in the insula in response to the unpleasant texture was positively correlated with social impairment as measured by the Autism Diagnostic Interview-Revised (ADI-R). These results suggest that people with ASD tend to show diminished response to pleasant and neutral stimuli, and exaggerated limbic responses to unpleasant stimuli, which may contribute to diminished social reward associated with touch, perpetuating social withdrawal, and aberrant social development.

Evaluation of a magnetic resonance-compatible dentoalveolar tactile stimulus device.

BACKGROUND: Few methods exist to study central nervous system processes following dentoalveolar tactile stimulation using functional magnetic resonance imaging (fMRI), likely due to inherent technical difficulties. Our primary goal was to develop and perform feasibility testing of a novel device capable of delivering valid and reliable dentoalveolar stimuli at dental chair-side and during MRI. Details of a device designed to deliver dentoalveolar dynamic pressure stimuli are described. Device testing took place in three settings: a) laboratory testing to assess range of stimulus force intensities, b) dental chair-side to assess reliability, validity and discriminant ability in force-pain relationship; and c) MRI to evaluate magnetic compatibility and ability to evoke brain activation in painfree subjects similar to those described in the literature. RESULTS: A novel device capable of delivering valid and reliable dentoalveolar somatosensory stimulation was developed (ICC = 0.89, 0.78-1 [95% CI]). Psychophysical data analysis showed high discriminant ability in differentiating painfree controls from cases with chronic dentoalveolar pain related to deafferenting dental procedures (sensitivity = 100%, specificity = 86.7%, area under ROC curve = 0.99). FMRI results of dentoalveolar dynamic pressure pain in painfree subjects revealed activation of brain areas typically associated with acute pain processing including thalamus, primary/secondary somatosensory, insular and prefrontal cortex. CONCLUSIONS: A novel psychophysical method to deliver dynamic dentoalveolar pressure stimulation was developed and validated, allowing non-invasive MRI-based exploration of central nervous system function in response to intraoral somatosensation. BACKGROUND: The organization of the trigeminal system is unique as it provides somatosensory innervation to the face, masticatory and oral structures, the majority of the intracranial contents 1 and to specialized structures (tongue, nasal mucosa, auricle, tympanic membrane, cornea and part of the conjunctiva) 2. Somatic sensory information transmitted by the trigeminal nerve is crucial for normal orofacial function; however, the mechanisms of many chronic pain conditions affecting areas innervated by this sensory system are not well understood 345. The clinical presentation of chronic intraoral pain in the area of a tooth or in a site formally occupied by a tooth with no clinical or radiological signs of pathology, referred to as atypical odontalgia (AO) 67, is one such chronic pain condition of particular interest to dentists that is difficult to diagnose and manage. Recent research suggests both peripheral and central nervous system mechanisms being involved in AO pathophysiology 8910, but the majority of mechanism-based research of patients with AO has focused on the "peripheral aspect" 7.Functional magnetic resonance imaging (fMRI) is an established research technique to study the central aspects of pain 11. Of existing neuroimaging techniques, fMRI provides good spatial resolution of cortical and subcortical structures critical in the processing of nociception, acceptable temporal resolution, does not involve ionizing radiation, and can be performed using most MRI systems that already exist in research centers and the community. For these reasons, we sought to develop a protocol that allows us to use this tool to investigate the central mechanisms involved in the processes of intraoral pain arising from the dentoalveolar region. Using this device, our long-term objective is to improve our understanding of the underlying mechanisms of persistent dentoalveolar pain.In the past few years several studies used fMRI to investigate the human trigeminal system 1213, with a limited subset focusing on intraoral stimulation - specifically on the dentoalveolar processes, such as lip, tongue and teeth stimulation 14 or only teeth 151617. Some reasons for scarce literature on this topic may be the technical challenges involved in delivering facial/intraoral stimulation inside a MR scanner 1718: possibility of magnetic interference, detriment of image quality, subject discomfort and reduced working space between the subject's head and the radiofrequency coil. As a consequence a MR-compatible device would need to not only overcome these challenges but also be capable of delivering a controlled and reproducible stimuli 19, as reliability/reproducibility is a necessary feature of sensory testing 20.Existing MR-compatible methods of dentoalveolar stimulation are limited and do not adequately deliver stimuli across a range of non-painful to painful intensities and/or cannot be adjusted to reach posterior aspects of the dentoalveolar region. Therefore our goal was to develop and test the feasibility of a device able to: 1) provide reliable and valid dentoalveolar stimuli, 2) deliver such stimulation within the restricted space of an MR head coil, 3) be compatible for use within an MR environment, and 4) produce brain activation in painfree controls consistent to those observed by others using fMRI.

Frequency of nonodontogenic pain after endodontic therapy: a systematic review and meta-analysis.

INTRODUCTION: Little is known about ill-defined pain that persists after endodontic procedures, including an estimate of the problem's magnitude. We conducted a systematic review of prospective studies that reported the frequency of nonodontogenic pain in patients who had undergone endodontic procedures. METHODS: Nonodontogenic pain was defined as dentoalveolar pain present for 6 months or more after endodontic treatment without evidence of dental pathology. Endodontic procedures reviewed were nonsurgical root canal treatment, retreatment, and surgical root canal treatment. Studies were searched in four databases electronically, complemented by hand searching. A summary estimate of nonodontogenic tooth pain frequency was derived using random-effects meta-analysis. RESULTS: Of 770 articles retrieved and reviewed, 10 met inclusion criteria, and nine had data on both odontogenic and nonodontogenic causes of pain. A total of 3,343 teeth were enrolled within the included studies and 1,125 had follow-up information regarding pain status. We identified 48 teeth with nonodontogenic pain and estimated a 3.4% (95% confidence interval, 1.4%-5.5%) frequency of occurrence. In nine articles containing data regarding both odontogenic and nonodontogenic causes of tooth pain, 56% (44/78) of all cases were thought to have a nonodontogenic cause. CONCLUSIONS: Nonodontogenic pain is not an uncommon outcome after root canal therapy and may represent half of all cases of persistent tooth pain. These findings have implications for the diagnosis and treatment of painful teeth that were previously root canal treated because therapy directed at the tooth in question would not be expected to resolve nonodontogenic pain.

Frequency of persistent tooth pain after root canal therapy: a systematic review and meta-analysis.

INTRODUCTION: Little is known about the frequency of persistent pain after endodontic procedures even though pain is a core patient-oriented outcome. We estimated the frequency of persistent pain, regardless of etiology, after endodontic treatment. METHODS: Persistent tooth pain was defined as pain present > or = 6 months after endodontic treatment. Endodontic procedures included in the review were pulpectomy, nonsurgical root canal treatment, surgical root canal treatment, and retreatment. Four databases were searched electronically complemented by hand searching. Two independent reviewers determined eligibility, abstracted data, and assessed study quality. A summary estimate of persistent all-cause tooth pain frequency was established by using a random-effects meta-analysis. Using subgroup analyses, we explored the influence of treatment approach (surgical/nonsurgical), longitudinal study design (prospective/retrospective), follow-up rate, follow-up duration, initial treatment versus retreatment, and quality of reporting (Strengthening the Reporting of Observational Studies in Epidemiology rankings) on the pain frequency estimate. RESULTS: Of 770 articles retrieved and reviewed, 26 met inclusion criteria. A total of 5,777 teeth were enrolled, and 2,996 had follow-up information regarding pain status. We identified 168 teeth with pain and derived a frequency of 5.3% (95% confidence interval, 3.5%-7.2%, p < 0.001) for persistent all-cause tooth pain. High and statistically significant heterogeneity among studies (I2 = 80%) was present. In subgroup analysis, prospective studies had a higher pain frequency (7.6%) than retrospectives studies did (0.9%). Quality of study reporting was identified as the most influential reason for study heterogeneity. CONCLUSIONS: The frequency of all-cause persistent tooth pain after endodontic procedures was estimated to be 5.3%, with higher report quality studies suggesting >7%.