Reliability of an intraoral extension for intraoral palpation and assessment of mechanical sensitivity of the temporal tendon.

BACKGROUND: The temporal tendon is a structure often compromised in patients suffering from temporomandibular disorders (TMD), yet its intraoral location makes a standardised assessment difficult. OBJECTIVES: To evaluate the variability and accuracy to target force of a newly designed intraoral extension for a palpometer device (Palpeter, Sunstar Suisse) when compared to manual palpation, in addition to clinically assessing the mechanical sensitivity and referred sensations of the temporal tendon in healthy individuals. METHODS: Experiment 1: 12 individuals were asked to target on a scale 0.5, 1 and 2 kg, for 2 and 5 s by using five different methods (Palpeter, Palpeter with three different extension shapes and manual palpation). Experiment 2: 10 healthy participants were recruited for a randomised double-blinded assessment by applying pressure of 0.5, 1 and 2 kg to the right temporal tendon with the three extensions and manual palpation. Participants rated the intensity of their sensation/pain on a 0-50-100 numeric rating scale (NRS), unpleasantness on a 0-100 NRS, and if present, they rated and drew the location of referred sensations. Repeated measures analysis of variance (ANOVA) was used in both experiments to compare differences between palpation methods. Tukey's HSD tests were used for the post hoc comparisons, and p values below .05 were considered significant. RESULTS: Experiment 1: The extensions showed no significant differences between them regarding reliability and accuracy for all forces and durations (p > .05). The manual method was significantly less reliable and accurate when compared to the other methods (p < .05). Experiment 2: There were no significant differences between the Palpeter extensions regarding pain intensity or unpleasantness NRS scores (p > .05), but all the extensions had significantly increased pain intensity and unpleasantness when compared to manual palpation (p < .05). Similarly, the frequency of referred sensations was similar between extensions but increased when compared to manual palpation. CONCLUSIONS: The new Palpeter extensions proved to be significantly more accurate and have lower test-retest variability than the manual method in a non-clinical setting. Clinically, they showed no significant differences in NRS scores for pain intensity nor unpleasantness, with no major differences in referred sensations, making any of the extensions suitable for clinical testing of the temporal tendon in future studies.

Mechanical sensitivity changes in pericranial muscles after local anesthesia and experimentally induced pain in the temporalis tendon: Implications for headache and facial pain.

OBJECTIVES: To assess changes in mechanical sensitivity of the pericranial muscles in healthy individuals after a local anesthetic block of the temporalis tendon. In addition, to assess, if experimentally induced temporalis tendon pain, can lead to an increase in mechanical sensitivity of the pericranial muscles and reports of headache. METHODS: 40 healthy participants were recruited for this randomized, double-blinded, controlled experiment, and were randomly injected with mepivacaine and isotonic saline into the dominant-side temporalis tendon in two different sessions, and either nerve growth factor (n = 20) or isotonic saline (n = 20) in a third session. Mechanical sensitivity was assessed in the temporalis, masseter, and trapezius muscles as well as in the temporalis tendon, on the dominant side, before and 10 minutes after each injection, and in a fourth session two days after the third session. Pain drawings and headache diaries were kept for 30 days after the final session to register any developing pain or headache. RESULTS: Mepivacaine injection into the temporalis tendon caused a significant decrease in mechanical sensitivity in the temporal tendon (-54.5%) and the masseter (-15.4%) muscle (P < 0.05) but not the temporalis (-12.1%) and trapezius muscles (-12.7%) (P > 0.05). Nerve growth factor injection into the temporalis tendon caused a significant increase in mechanical sensitivity in the tendon (+15.4%) and masseter muscle (+14.4%) (P < 0.05) but not the temporalis (+2.8%) or trapezius muscles (+3.1%) (P > 0.05). A significant increase was found for headache frequency in the first seven days (P < 0.05) after nerve growth factor injection compared to after isotonic saline injection, but not intensity (P > 0.05). CONCLUSION: These findings suggest that the therapeutic effect of temporalis tendon anesthetic injections on facial pain and headaches are most likely not only due to a direct effect of the local anesthetic on the temporalis tendon but rather to a more generalized block of the nerves in the area. In addition, the temporal tendon may contribute to the pathophysiological processes of headache.

Pain in the temple? Headache, muscle pain or both: A retrospective analysis.

AIM: Headache attributed to temporomandibular disorders and myalgia are two diagnoses included in the diagnostic criteria for temporomandibular disorders (DC/TMD). However, it is not clear if these two diagnoses are different clinical entities given their similar presentation and way in which they are diagnosed, when the myalgia is within the temporalis muscle. The purpose of this retrospective study was to assess the overlap between headache attributed to temporomandibular disorders and myalgia of the temporalis muscle. METHODS: The charts of 671 patients seeking treatment at the Section of Orofacial Pain and Jaw Function, Aarhus University, Denmark, between January 2015 and February 2020 were screened for a diagnosis of headache attributed to temporomandibular disorders, myalgia of the temporalis muscle, or both. RESULTS: A total of 89 patients fulfilled the DC/TMD criteria for either headache attributed to TMD, myalgia of the temporalis or both. Of these, two had a diagnosis of headache attributed to TMD, 16 of myalgia of the temporalis, and 71 were diagnosed with both. In 97.3% of the times that headache attributed to temporomandibular disorders was diagnosed, the patient was also diagnosed with myalgia of the temporalis. The Jaccard index was 0.8, indicating a substantial overlap between the two diagnoses. Finally, the overlap of pain location between the two diagnoses was substantial, with a Jaccard index of 0.9. CONCLUSIONS: In the present study, headache attributed to temporomandibular disorders was almost exclusively diagnosed together with myalgia of the temporalis. Therefore, we propose that headache attributed to temporomandibular disorders and myalgia of the temporalis muscle have more clinical similarities than differences and as such could be considered one single clinical entity. Further studies will be needed to address the clinical consequences of this proposal.

Assessment of Pain Modulatory and Somatosensory Profiles in Chronic Tension-Type Headache Patients.

OBJECTIVE: The aim of this study was to thoroughly phenotype a group of chronic tension-type headache (CTTH) patients. METHODS: Fifteen CTTH patients diagnosed according to the International Classification of Headache Disorders-3 and 15 healthy controls were included in this study. Furthermore, 70 healthy controls were included to establish normative values. Quantitative sensory testing (QST), including temporal summation of pain (TSP), conditioned pain modulation (CPM), and psychological and sleep variables, was assessed in a single session. TSP and CPM were then combined to build pain modulation profiles (PMP) for each individual. RESULTS: No difference was found between groups for PMP, TSP, and CPM. However, 10 CTTH patients showed a pronociceptive PMP, with 8 related to a deficient CPM and 2 to both a deficient CPM and increased TSP. Increased cold detection thresholds were the most common sensory disturbance found in CTTH patients. Significant differences were seen between groups for pain catastrophizing, depression, and sleep quality although not all patient's scores were above the clinically meaningful cutoffs. CONCLUSIONS: In summary, CTTH patients presented with different PMP. These PMP may be related to increased TSP, deficient CPM, alterations in thermal detection that may be related to autonomic dysregulation, or a combination of all three. Overall, this suggests that due to their heterogeneous pathophysiology, CTTH patients should be managed according to their underlying pathophysiology and not with a one-size-fits-all approach.

Interprofessional Collaboration in Dentistry: Role of physiotherapists to improve care and outcomes for chronic pain conditions and sleep disorders.

Physiotherapists can manage chronic pain patients by using technical interventions such as mobility, strengthening, manual therapy, or flexibility in a specific and functional manner, being a key component of a multidisciplinary team. Dentists are involved in the management of different chronic pain conditions such as temporomandibular disorders and sleep disorders such as obstructive sleep apnea. However, they are frequently unaware of the benefits of collaborating with physical therapists. In this review, the collaboration of physical therapists and dentists will be explored when managing orofacial pain, headaches, and sleep disorders. The physical therapist is important in the management of these disorders and also in the screening of risk factors.

Characterization and predictive mechanisms of experimentally induced tension-type headache.

OBJECTIVE: Studies have shown it is possible to elicit a tension-type headache episode in 15 to 30% of healthy individuals following a tooth-clenching or stress-inducing task. Despite this, no studies have attempted to understand why some healthy individuals develop a headache episode while others do not. METHODS: The present randomized, single-blind, controlled study recruited 60 healthy participants who participated in a 30-minute tooth-clenching task and 10 participants who participated in a control task. Before the tasks, participants had their pericranial tenderness and pain modulation profiles (wind-up ratio and conditioned pain modulation) assessed. Two hours later, pericranial tenderness and pressure pain thresholds were assessed as well as any developing temporomandibular disorders. Pain diaries were kept for 24 hours to register any developing pain or headache. RESULTS: Participants with a decrease in pericranial tenderness after the tooth-clenching task were less likely to develop headache when compared to participants without. Pain modulation profiles could not predict who developed headache and who did not. Finally, no difference was found between groups for developing temporomandibular disorders. No difference in frequency of participants who developed headache was found between the tooth-clenching and the control task. CONCLUSIONS: In conclusion, it was shown that increased pericranial tenderness was not required to trigger an episode of tension-type headache in healthy participants. Furthermore, pain modulation profiles could not predict who developed headache and who did not. Finally, activation of descending inhibitory pathways, as assessed by decreases in pericranial tenderness, was protective against the development of headache. These findings provide new insights into the pathophysiology of experimentally-induced tension-type headache.

Association of risk assessment at diagnosis with healthcare resource utilization and health-related quality of life outcomes in pulmonary arterial hypertension.

We aimed to describe the clinical characteristics, healthcare resource utilization (HCRU) and costs, health-related quality of life (HRQoL), and survival for patients with pulmonary arterial hypertension (PAH), stratified by 1-year mortality risk at diagnosis. Adults diagnosed with PAH at the Sheffield Pulmonary Vascular Disease Unit between 2012 and 2019 were included. Patients were categorized as low, intermediate, or high risk for 1-year mortality at diagnosis. Demographics, clinical characteristics, comorbidities, HCRU, costs, HRQoL, and survival were analyzed. Overall, 1717 patients were included: 72 (5%) at low risk, 941 (62%) at intermediate risk, and 496 (33%) at high risk. Low-risk patients had lower HCRU prediagnosis and 1-year postdiagnosis than intermediate- or high-risk patients. Postdiagnosis, there were significant changes in HCRU, particularly inpatient hospitalizations and accident and emergency (A&E) visits among high-risk patients. At 3 years postdiagnosis, HCRU for all measures was similar across risk groups. Low-risk patients had lower EmPHasis-10 scores (indicating better HRQoL) at diagnosis and at 1-year follow-up compared with intermediate- and high-risk patients; only the score in the high-risk group improved. Median overall survival decreased as risk category increased in analyzed subgroups. Low-risk status was associated with better 1-year survival and HRQoL compared with intermediate- and high-risk patients. HCRU decreased in high-risk patients postdiagnosis, with the most marked reduction in A&E admissions. The pattern of decreased per-patient inpatient hospitalizations and A&E visits at 3 years postdiagnosis suggests that a diagnosis of PAH helps to decrease HCRU in areas that are key drivers of costs.

Risk assessment and real-world outcomes in chronic thromboembolic pulmonary hypertension: insights from a UK pulmonary hypertension referral service.

OBJECTIVES: This study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Retrospective observational study. SETTING: Pulmonary hypertension referral centre in the UK. PARTICIPANTS: Adults diagnosed with CTEPH between 1 January 2012 and 30 June 2019 were included. Cohorts were retrospectively defined for operated patients (received pulmonary endarterectomy (PEA)) and not operated; further subgroups were defined based on risk score (low, intermediate or high risk for 1-year mortality) at diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographics, clinical characteristics, comorbidities, treatment patterns, HRQoL, HCRU, costs and survival outcomes were analysed. RESULTS: Overall, 683 patients were analysed (268 (39%) operated; 415 (61%) not operated). Most patients in the operated and not-operated cohorts were intermediate risk (63%; 53%) or high risk (23%; 31%) at diagnosis. Intermediate-risk and high-risk patients had higher HCRU and costs than low-risk patients. Outpatient and accident and emergency visits were lower postdiagnosis for both cohorts and all risk groups versus prediagnosis. HRQoL scores noticeably improved in the operated cohort post-PEA, and less so in the not-operated cohort at 6-18 months postdiagnosis. Survival at 5 years was 83% (operated) and 49% (not operated) and was lower for intermediate-risk and high-risk patients compared with low-risk patients. CONCLUSIONS: Findings from this study support that risk assessment at diagnosis is prognostic for mortality in patients with CTEPH. Low-risk patients have better survival and HRQoL and lower HCRU and costs compared with intermediate-risk and high-risk patients.

Referred sensation location can be altered by a strong heterotopic nociceptive stimulus: implications for clinical pain conditions.

ABSTRACT: Referred sensations (RS) are a common clinical phenomenon in patients with musculoskeletal pain; however, the underlying mechanisms of RS and implications for diagnosis and management are poorly understood. The location of referral seems to have a preferred site, but studies have suggested it can be redirected to a site of previous injury and pain. However, it is not known if the same phenomenon can occur for a much shorter-lasting painful stimulus in the trigeminal system. The aim of this study was to assess if RS location elicited with standardized palpation of the masseter muscle could be altered following a 10-minute painful infusion of hypertonic saline into the retromolar region. A total of 56 healthy participants participated in this cross-over study performed in 2 sessions separated by 1 hour. At each session, baseline and postinfusion assessments of masseter muscle mechanical sensitivity were performed using 2 different forces (0.5 kg and 2 kg). Between assessments, hypertonic saline (5%) or isotonic saline (control) were continuously infused into the retromolar region. Participants were asked to rate their mechanical sensitivity and any RS they experienced as well as to draw the location of the RS. No difference in mechanical sensitivity or RS frequency was seen after either infusion when compared with before infusion. However, the RS location was displaced on average 1.2 cm between the baseline and postinfusion assessments for the hypertonic saline infusion, which was significantly increased when compared with the isotonic saline infusion which was on average 0.4 cm. These novel findings indicate the potential to modify the location of RS in the trigeminal system following a relatively brief noxious input. Clinicians need to be aware of the possible rerouting of RS in patients with complex orofacial pain.

Referred sensations in the orofacial region are associated with a decreased descending pain inhibition and modulated by remote noxious stimuli and local anesthesia.

ABSTRACT: Referred sensation (RS) as a specific clinical phenomenon has been known for a long time, although the underlying mechanisms remain unclear. The aims of this study were to assess if (1) healthy individuals who experienced RS had a less active endogenous pain system when compared with those who did not; (2) activation of descending pain inhibition mechanisms can modulate RS parameters; and finally, (3) a transient decrease in peripheral afferent input because of a local anesthetic (LA) block in the masseter muscle can modulate RS parameters. To assess these, 50 healthy participants were assessed in 3 different sessions. In the first session, conditioned pain modulation (CPM) as well as mechanical sensitivity and RS at the masseter muscle were assessed. In the same session, participants who experienced RS had their mechanical sensitivity and RS assessed again while undergoing a CPM protocol. In the second and third sessions, participants had their mechanical sensitivity and RS assessed before and after receiving an injection of 2 mL of LA and isotonic saline into the masseter muscle. The main findings of this study were (1) participants who experienced RS during standardized palpation exhibited increased mechanical sensitivity ( P < 0.05, Tukey post hoc test) and decreased CPM ( P < 0.05, Tukey post hoc test) when compared with those who did not; RS incidence ( P < 0.05, Cochran Q test), frequency ( P < 0.05; Friedman test), intensity ( P < 0.05, Tukey post hoc test), and area ( P < 0.05, Tukey post hoc test) were all significantly reduced when assessed (2) during a painful conditioning stimulus and (3) after LA block. These novel findings highlight that RS in the orofacial region are strongly modified by both peripheral and central nervous system factors.

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.

Effect of standardized training in combination with masseter sensitization on corticomotor excitability in bruxer and control individuals: a proof of concept study.

Recently, it has been proposed that bruxism could represent an overlearned behavior due to the absence of corticomotor plasticity following a relevant tooth-clenching task (TCT). This study assessed the modulatory effects of a nerve growth factor (NGF) injection on masseter muscle corticomotor excitability, jaw motor performance, pain, and limitation in bruxer and control participants following a TCT. Participants characterized as definitive bruxers or controls were randomly assigned to have injected into the right masseter muscle either NGF or isotonic saline (IS), resulting in a study with 4 arms: IS_Control (n = 7), IS_Bruxer (n = 7); NGF_Control (n = 6), and NGF_Bruxer (n = 8). The primary outcome was the masseter motor evoked potential (MEP) amplitude measured at baseline and after a TCT. After the interventions, significantly higher and lower MEP amplitude and corticomotor map area were observed, respectively, in the IS_Control and NGF_Control groups (P < 0.05). Precision and accuracy depended on the series and target force level with significant between-group differences (P < 0.01). NGF-induced masseter muscle sensitization, in combination with a training-induced effect, can significantly impact the corticomotor excitability of the masseter muscle in control participants indicating substantial changes in corticomotor excitability, which are not observed in bruxers. These preliminary findings may have therapeuthic implications for the potential to "detrain" and manage bruxism, but further studies with larger sample sizes will be needed to test this new concept.

Location of mechanically-evoked referred sensations within the trigeminal region are not altered following a heterotopic painful stimulus.

To investigate whether the location, area and frequency of referred sensations occurring during palpation of the masseter muscle can be influenced by application of a conditioning painful stimulus to the temporalis muscle. Thirty healthy participants were included in this cross-over study, performed in two sessions with > 48 h in between. At each session, palpation of the masseter muscle was performed before and after 0.2 ml of glutamate (1 mol/L) or isotonic saline (control) were injected into the anterior portion of the temporalis muscle. Palpation of the masseter muscle was done using four different forces (0.5 kg, 1 kg, 2 kg and 4 kg). Participants rated the perceived intensity of the palpation and any referred sensations on a 0-50-100 numeric rating scale, the perceived pain intensity following the injections on an electronic visual analogue scale and drew any referred sensations they experienced. No difference in referred sensations location, area and frequency was shown r during palpation either before or after injections (P > 0.05). A moderate correlation was found between perceived sensation scores and referred sensations intensity for the temporalis muscle following glutamate injection (r = 0.407, P < 0.05). Moreover, significantly more participants reported referred sensations for glutamate injections into the temporalis muscle when compared to isotonic saline (P < 0.05). Finally, a significant decrease in the perceived intensity of palpation of the masseter muscle was seen after glutamate injection in the temporalis muscle (P < 0.05). In the current study, location, area and frequency of referred sensations following mechanical stimulation of the masseter muscle were not altered by the application of a painful stimulus to the temporalis muscle. In addition, there seems to be a positive relationship between painful stimuli and referred sensations frequency and intensity elicited from the temporalis muscle.

Is bruxism associated with changes in neural pathways? A systematic review and meta-analysis of clinical studies using neurophysiological techniques.

This study aimed to systematically review the literature to identify clinical studies assessing neuroplasticity changes induced by or associated with bruxism or a tooth-clenching task using neurophysiological techniques. Searches were performed in five electronic databases (PubMed, EMBASE, Scopus, Web of Science, and Google Scholar) in April 2020. This review included clinical studies using neurophysiological techniques to assess neuroplasticity changes in healthy participants before and after a tooth-clenching task or comparing bruxers and non-bruxers. The quality assessment was performed with the Joanna Briggs Institute tool and Grading of Recommendations Assessment, Development, and Evaluation. Meta-analyses were conducted with studies reporting similar comparisons regarding masseter motor evoked potential amplitude and signal change outcomes. Of 151 articles identified in the searches, nine were included, and five proceeded to meta-analysis. Included studies presented moderate to very low methodological quality. From these included studies, eight evaluated bruxers and non-bruxers, of which five of them observed brain activity differences between groups, and three found no differences. Even so, all studies have suggested distinct difference in the central excitability between bruxers and non-bruxers, the meta-analysis revealed no statistically significant differences (P > 0.05). It appears that bruxism seems, indeed, to be associated with distinct differences in the neural pathways related to the control of the jaw-closing muscles, but that considerable variability in terms of classification of bruxism and assessment of neuroplasticity hamper a definite conclusion. Future research projects should take these concerns into consideration in order to further the understanding of bruxism physiology and pathophysiology.

Peripheral N-methyl-D-aspartate receptor activation contributes to monosodium glutamate-induced headache but not nausea behaviours in rats.

Monosodium glutamate induces behaviors thought to reflect headache and nausea in rats. We explored the effects of the N-methyl-D-aspartate receptor antagonist (2R)-amino-5-phosphonovaleric acid, the inotropic glutamate receptor antagonist kynurenic acid, and the CGRP receptor antagonist olcegepant, on monosodium glutamate-induced increases in nocifensive, headache-like and nausea behaviours. Effects of these antagonists on motor function were examined with a rotarod. The effect of the dopamine receptor antagonist metoclopramide and the serotonin 3 receptor antagonist ondansetron on nausea behaviour was also assessed. (2R)-amino-5-phosphonovaleric acid, and to a lesser extent, kynurenic acid and olcegepant, reduced nocifensive and headache-like behaviours evoked by monosodium glutamate. No alteration in motor function by (2R)-amino-5-phosphonovaleric acid, kynurenic acid or olcegepant was observed. No sex-related differences in the effectiveness of these agents were identified. Nausea behaviour was significantly more pronounced in male than in female rats. Olcegepant, ondansetron and metoclopramide ameliorated this nausea behaviour in male rats. Ondansetron and metoclopramide also reduced headache-like behaviour in male rats. These findings suggest that peripheral N-methyl-D-aspartate receptor activation underlies monosodium glutamate-induced headache-like behaviour but does not mediate the nausea behaviour in rats.

Systemic administration of monosodium glutamate induces sexually dimorphic headache- and nausea-like behaviours in rats.

ABSTRACT: Ingestion of monosodium glutamate (MSG) causes headache, nausea, and craniofacial tenderness in healthy individuals. The present study explored whether MSG produces behavioural signs of headache, nausea, and changes in craniofacial sensitivity in rats. The behavior of male and female Sprague-Dawley rats was video recorded before and after intraperitoneal (i.p.) injections of MSG (1-1000 mg/kg), nitroglycerin (GTN, 10 mg/kg), or normal saline. Behaviors (grimace score, head-flicks, rearing, head scratches, facial grooming, lying-on-belly, and temporalis muscle region mechanical withdrawal threshold) were evaluated. Facial cutaneous temperature of the nose and forehead was measured before and after i.p. injections via infrared thermography. Plasma glutamate and calcitonin gene-related peptide concentrations after administration of 1000 mg/kg MSG were measured in anesthetized rats. Monosodium glutamate induced nocifensive, headache-like, and nausea-like behaviors in a dose-related manner but had no effect on mechanical threshold. Monosodium glutamate (1000 mg/kg) induced a significantly greater frequency of headache-like behavior in females but a longer duration of nausea-like behavior in males. Monosodium glutamate produced a prolonged increase in plasma glutamate and calcitonin gene-related peptide concentrations. Co-administration of the median effective dose of MSG (350 mg/kg) with GTN (10 mg/kg) amplified headache-like behaviors, induced significant craniofacial sensitivity, and produced increased nausea-like behaviour. Co-administration of sumatriptan or naproxen with MSG (1000 mg/kg) significantly attenuated MSG-induced nocifensive and headache-like behaviors. Our data suggest that systemic administration of MSG to rats induces behavioral correlates of headache and nausea. This model may offer another avenue for research on the mechanism and treatment of primary headache disorders such as migraine.

Healthcare resource utilization and quality of life in patients with sarcoidosis-associated pulmonary hypertension.

A retrospective, observational cohort study was conducted to generate real-world evidence in adult patients diagnosed with sarcoidosis-associated pulmonary hypertension (SAPH) at a referral center in England between 2012 and 2019. Data from the referral center electronic medical record database were linked to the National Health Service Hospital Episode Statistics database to collect and analyze patient demographics, clinical characteristics, comorbidities, treatment patterns, health-related quality of life (HRQoL; assessed using the EmPHasis-10 questionnaire), healthcare resource utilization (HCRU), costs, and survival. Sixty-two patients with SAPH were identified. At diagnosis, 84% were in WHO functional class III and presented with significant pulmonary hemodynamic impairment. Cardiovascular and respiratory comorbidities were commonly reported prediagnosis. Median EmPHasis-10 score at diagnosis was 34, indicative of poor HRQoL. In the 1st year after diagnosis, median (Q1, Q3) per-patient HCRU was 1 (0, 2) all-cause inpatient hospitalizations; 3 (2, 4) same-day hospitalizations; and 9 (6, 11) outpatient consultations. In 24 patients who were hospitalized longer than 1 day in the 1st year after diagnosis, the median duration of hospitalization was 4 days. With a median follow-up of 1.8 years, the median overall survival was 2.9 years. In this cohort of patients with SAPH, poor HRQoL and high HCRU were observed following diagnosis. To our knowledge, this is the first study to report on HRQoL and HCRU in patients with SAPH. More research is needed on treatment options for this population with high unmet needs.

Remote physical examination for temporomandibular disorders.

ABSTRACT: There is a need to further develop telemedicine approaches because of the immediate and perhaps long-term consequences of the coronavirus disease 2019. Thus, a remote protocol for assessment of patients with temporomandibular disorders (TMD) was developed, and the agreement of this protocol was compared with the guidelines of the Diagnostic Criteria for TMD (DC/TMD). A total of 16 individuals were first assessed by a reference standard examination (RSE) and 3 other examinations applied in a random order by 3 examiners: standard physical examination (standard examination), physical examination keeping 2-m distance (physical distanced examination), and examination conducted with the aid of video communication technology (video communication examination). The primary outcomes were the diagnoses of myalgia of the masseter and temporalis muscles and arthralgia. The diagnoses of intra-articular joint disorders were considered secondary outcomes because of a less impact on psychosocial functioning and quality of life when compared with the pain-related diagnoses. The Fleiss kappa coefficient and its 95% confidence interval were computed to determine the level of agreement in diagnoses between each examination protocol and the RSE. There was substantial to almost perfect agreement between the RSE and all the examination protocols for the diagnoses of myalgia (0.86-1.00) and arthralgia (0.74-0.87) (P < 0.001). On the other hand, there was an overall poor agreement (0.30-0.58) between the RSE and all the protocols for the diagnosis of disk displacement with reduction. Remote assessment of patients with pain-related TMD is feasible and presents a high degree of accuracy.

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.