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(1) To deepen knowledge on how specialized health care professionals (HCPs) reflect on encounters with children diagnosed with juvenile idiopathic arthritis (JIA) and (2) to outline a theory for orofacial care.Grounded theory was used to discover the psychosocial processes involved in communication between HCPs, children, and parents, and this information was used to develop a theory about these processes. Using classic grounded theory, a total of 20 interviews with HCPs were analyzed.One main concern, "secure health and biopsychosocial development," permeated all care. A core category was identified as "create a responsive interaction with the child and family." The data that supported this core category helped to explain how the HCP responded to a patient to promote orofacial health. Based on the dentist's responses to the child, eight subcategories were identified: (1) secure confidential relationships; (2) convey disease-specific knowledge; (3) communicate healthy findings and form mutual insights at examination; (4) encourage health-promoting behaviors; (5) ensure follow-up; (6) share perspectives; (7) guide parenting; and (8) improve knowledge and networks.How the dentist shall best understand the needs of a child diagnosed with JIA requires further evaluation. To promote oral health, the child must feel safe, confirmed, and supported with knowledge. Also, further studies are needed on the dentist's collaboration with the pediatrician and the physiotherapist for contributing to overall health.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

The aims of this study were (1) to compare the levels and interactions of several plasma proteins in patients with myogenous temporomandibular disorders (TMDM) compared to healthy and pain-free controls, (2) to compare the levels and interactions in two TMDM subgroups, myalgia (MYA) and myofascial pain (MFP), and (3) to explore associations between the proteins and clinical data. Thirty-nine patients with TMDM (MFP

Background The clinical care of chronic pain requires personalised understanding of the mechanisms involved. Temporomandibular disorders (TMD) are the most common chronic orofacial pain conditions, and oxidative stress has been proposed to be implicated in their pathophysiology, especially in arthrogenous TMD. However, few studies have explored oxidative stress in myogenous TMD (TMDM). Objective The aims of this study were to compare the salivary oxidative stress profiles between individuals with TMDM and healthy controls, and to explore associations of these markers with clinical characteristics. Methodology Saliva samples were collected from 39 individuals with TMDM and 37 age and sex-matched healthy volunteers. Psychological stress levels and clinical characteristics were assessed in all participants. The samples were analysed for total oxidant status (TOS), total antioxidative capacity (TAC) and superoxide dismutase activity (SODa). Comparisons between groups were performed using parametric and non-parametric tests depending on data distribution. Results Psychological stress was higher in TMDM compared to controls (P < .001). TAC levels were significantly higher (P < .05) whereas TOS levels were significantly lower (P < .05) in TMDM compared to controls. There were no differences in SODa levels between groups and no correlations were found between clinical characteristics and oxidative stress markers. Conclusion Individuals with TMDM showed higher levels of antioxidative markers, but lower levels of oxidative markers. These results can be explained in part by chronicity and adaptation to the disease and other factors, such as psychological stress. Longitudinal studies must be conducted to clarify the role of oxidative stress in TMDM. Funding Agencies|Swedish Research CouncilSwedish Research Council [K2009-52P-20943-03-2, 2014-2979]; Stockholm County CouncilStockholm County Council; Karolinska Institutet (ALF project); Karolinska Institutet (SOF project); Swedish Dental Society; Swedish Rheumatism Association

Background In skeletal muscle, free nerve endings are mostly located within the connective tissue. However, the distribution of sensory afferent fibres in healthy human masseter muscle tissues has not been studied. Objectives Primarily to investigate human masseter muscle nerve fibre densities as well as expression of NR2B receptors, substance P (SP) and nerve growth factor (NGF), and secondarily to compare this between a) nerve fibres associated with myocytes and within connective tissue; b) sexes; and c) ages. Methods Microbiopsies of the masseter muscle were obtained from 60 sex‐ and age‐matched healthy participants. Biopsy sections were analysed using immunohistochemistry and were visualised with a Leica TCS SPE confocal microscope. The Mann‐Whitney U test was used for statistical analyses. Results The density of nerve fibres within connective tissue was significantly greater than in nerve fibres associated with myocytes (P

Background Different pain syndromes may be characterized by different profiles of mediators reflecting pathophysiological differences, and these alterations may be measured in a simple saliva sample. The aims of the current study were to compare concentration of glutamate, serotonin (5-HT), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and substance P (SP) in saliva and plasma from a well-defined group of patients with chronic temporomandibular disorders myalgia (TMD-myalgia) with a group of pain-free controls, and further investigate the relationship between these markers and clinical characteristics. Methods Patients diagnosed according to the diagnostic criteria for TMD (n = 39), and matched healthy pain-free controls (n = 39) were included. Stimulated whole saliva and plasma samples were collected in the morning. Glutamate was analysed using a colorimetric assay, and 5-HT and SP were analysed by commercially available ELISA. Levels of NGF and BDNF were determined using multiplex electrochemiluminescence assay panel. Results Patients expressed higher salivary and plasma levels of glutamate (saliva: 40.22 ± 13.23 μmol/L; plasma: 30.31 ± 18.73 μmol/L) than controls (saliva: 33.24 ± 11.27 μmol/L; plasma: 20.41 ± 15.96 μmol/L) (p p p Conclusion The higher levels of salivary and plasma glutamate in patients with TMD-myalgia compared to controls strengthens its importance in the pathophysiology of TMD-myalgia. However, the lack of correlation to pain levels question its role as a putative biomarker. Patients with TMD-myalgia further had lower levels of salivary NGF and BDNF, but higher plasma BDNF. These results and their correlations to psychological distress warrant further investigations.

Background Music is used to evoke audio analgesia during dental procedures, but it is unknown if experimental pain and music interact. This study aimed to explore the multisensory interaction between contrasting types of music and experimentally induced muscle pain. Methods In 20 healthy women, 0.3 mL sterile hypertonic saline (5.8%) was injected into the masseter muscle during three sessions while contrasting music (classical and black metal) or no music was played in the background. Pain intensity was assessed every 15 seconds with a 0-100 mm visual analogue scale (VAS) until pain subsided. Pain spread (pain drawings), unpleasantness (VAS), anxiety (VAS), and pain quality (McGill Questionnaire) were assessed after the last pain assessment. Results Pain of high intensity was evoked at all sessions with a median (interquartile range) peak pain intensity of 78 (30) in the black metal music, 86 (39) in the classical music, and 77 (30) in the control session. The pain duration was 142 (150) seconds in the black metal music, 135 (150) seconds in the classical music, and 135 (172) seconds in the control session. The corresponding pain-drawing areas were 42 (52), 37 (36), and 44 (34), arbitrary units respectively. There were no differences in any of these variables (Friedman's test; P´s > .368), or in unpleasantness, anxiety, or pain quality between sessions (P´s > .095). Conclusions Experimentally induced muscle pain does not seem to be influenced by contrasting types of background music. Further studies exploring the multisensory integration between music and experimental muscle pain are needed.

PURPOSE Physical exercise is increasingly being promoted by health care for chronic pain conditions with beneficial outcomes, such as pain and fatigue reduction, and increased quality of life. Nevertheless, knowledge about biochemical consequences of physical exercise in chronic pain is still relatively poor. The endocannabinoid system has been suggested to play a role for acute exercise-induced reward and pain inhibition. The aim of this study is to investigate the chronic outcomes of resistance exercise on levels of endocannabinoids and related lipids in fibromyalgia (FM). METHODS This study examine the outcomes of a 15-wk person-centered resistance exercise program on plasma levels of the lipid mediators; anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide (SEA) sampled from 37 women with FM and 33 healthy controls. The associations between clinical scorings of pain, depression, anxiety, fatigue, and muscle strength with levels of these lipid mediators before and after the exercise program are also analyzed. RESULTS After the 15-wk exercise program, anandamide levels were significantly increased, and SEA levels significantly decreased in FM. Pain intensity and depression scorings decreased and muscle strength increased, and in a multivariate context, muscle strength was positively associated with 2-AG levels after the resistance exercise program in FM. CONCLUSIONS The increased anandamide and decreased SEA in women with FM after the 15-wk program might point to a chronic effect of resistance exercise. Pain and depression scorings decreased in the FM group after the program, but no associations between pain, depression, and lipid level changes were assured.

Supplemental digital content is available in the text., Purpose Fibromyalgia (FM) is a complex pain condition, and exercise is considered the first option of treatment. Few studies have examined the effect of exercise on molecular mechanisms in FM. The aim of this study was to analyze the plasma proteome in women with FM and healthy controls (CON) before and after 15 wk of resistance exercise. This study further investigated whether clinical and exercises-related outcomes correlated with identified plasma proteins in FM. Methods Plasma samples from 40 FM/25 CON (baseline) and 21 FM/24 CON (postexercise) were analyzed using shotgun proteomics. Clinical/background data were retrieved through questionnaires. Exercise-related variables and pressure pain thresholds were assessed using standardized instruments. Multivariate statistics were applied to analyze the proteomic profile at baseline and postexercise, and correlation with clinical/exercise-related data. Results Fifteen weeks of resistance exercises improved clinical symptoms and muscle strength, and affected circulating proteins related to immunity, stress, mRNA stability, metabolic processes, and muscle structure development in FM. Pressure pain threshold was related to a specific protein profile, with proteins involved in metabolic and immune response. Subgroups of FM based on plasma proteins, FM duration, and improved muscle strength were identified. Conclusions Exercise seems to affect circulating proteins, clinical characteristics, and muscle strength in FM. This study contributes to better understanding of systemic protein changes in FM compared with CON and how resistance exercise affects such changes.

IntroductionAbout 20% of the adult population have chronic pain, often associated with psychological distress, sick leave and poor health. There are large variations in the clinical picture. A biopsychosocial approach is used in investigation and treatment. The concept of personalised medicine, that is, optimising medication types and dosages for individual patients based on biomarkers and other patient-related factors, has received increasing attention in different diseases but used less in chronic pain. This cooperative project from all Swedish University Hospitals will investigate whether there are changes in inflammation and metabolism patterns in saliva and blood in chronic pain patients and whether the changes correlate with clinical characteristics and rehabilitation outcomes.Methods and analysisPatients at multidisciplinary pain centres at University Hospitals in Sweden who have chosen to participate in the Swedish Quality Registry for Pain Rehabilitation and healthy sex-matched and age-matched individuals will be included in the study. Saliva and blood samples will be collected in addition to questionnaire data obtained from the register. From the samples, proteins, lipids, metabolites and micro-RNA will be analysed in relation to, for example, diagnosis, pain characteristics, psychological distress, body weight, pharmacological treatment and clinical rehabilitation results using advanced multivariate data analysis and bioinformatics.Ethics and disseminationThe study is approved by the Swedish Ethical Review Authority (Dnr 2021-04929) and will be conducted in accordance with the declaration of Helsinki.The results will be published in open access scientific journals and in popular scientific relevant journals such as those from patient organisations. Data will be also presented in scientific meetings, meeting with healthcare organisations and disseminated in different lecturers at the clinics and universities. Funding Agencies|Petrus and Augusta Hedlunds Foundation; Gun and Bertil Stohnes Foundation; Loo and Hans Osterman Foundation; Demens foundation; Brain foundation [FO2018-0315]; Senil demens Sarfond foundation Region Orebro; Gamla Tjanarinnor foundation; Swedish Research Council [2018-02470]; Research-ALF region Ostergotland [RO-834951]

Nocifensive behavior induced by injection of glutamate or nerve growth factor (NGF) into rats masseter muscle is mediated, in part, through the activation of peripheral NMDA receptors. However, information is lacking about the mechanism that contributes to pain and sensitization induced by these substances in humans. Immunohistochemical analysis of microbiopsies obtained from human masseter muscle was used to investigate if injection of glutamate into the NGF-sensitized masseter muscle alters the density or expression of the NMDA receptor subtype 2B (NR2B) or NGF by putative sensory afferent (that express SP) fibers. The relationship between expression and pain characteristics was also examined. NGF and glutamate administration increased the density and expression of NR2B and NGF by muscle putative sensory afferent fibers (P

The neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sex-related differences in its effect are not well understood in humans. Therefore, this longitudinal cohort study aimed to investigate the effect of NGF injection on the density and expression of substance P, NMDA-receptors and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics, and to determine any possible sex-related differences in these effects of NGF. The magnitude of NGF-induced mechanical sensitization and pain during oral function was significantly greater in women than in men (P s = 0.620, P = 0.048), and expression of NMDA-receptors by putative nociceptors and change in temporal summation pain after glutamate injection (rs = 0.561, P = 0.003). In women, there was a significant inverse relationship between the degree of NGF-induced mechanical sensitization and the change in nerve fiber expression of NMDA-receptors alone (rs = − 0.659, P = 0.013), and in combination with NGF (rs = − 0.764, P = 0.001). In conclusion, women displayed a greater magnitude of NGF-induced mechanical sensitization that also was associated with nerve fibers expression of NMDA-receptors, when compared to men. The present findings suggest that, in women, increased peripheral NMDA-receptor expression could be associated with masseter muscle pain sensitivity.

AIMS: To investigate whether an international consensus exists among TMD experts regarding indications, performance, follow-up, and effectiveness of jaw exercises. METHODS: A questionnaire with 31 statements regarding jaw exercises was constructed. Fourteen international experts with some geographic dispersion were asked to participate in this Delphi study, and all accepted. The experts were asked to respond to the statements according to a 5-item verbal Likert scale that ranged from "strongly agree" to "strongly disagree." The experts could also leave free-text comments, which was encouraged. After the first round, the experts received a compilation of the other experts' earlier responses. Some statements were then rephrased and divided to clarify the essence of the statement. Subsequently, the experts were then asked to answer the questionnaire (32 statements) again for the second round. Consensus was set to 80% agreement or disagreement. RESULTS: There is consensus among TMD experts that jaw exercises are effective and can be recommended to patients with myalgia in the jaw muscles, restricted mouth opening capacity due to hyperactivity in the jaw closing muscles, and disc displacement without reduction. The patients should always be instructed in an individualized jaw exercise program and also receive both verbal advice and written information about the treatment modality. CONCLUSION: This Delphi study showed that there is an international consensus among TMD experts that jaw exercises are an effective treatment and can be recommended to patients with TMD pain and disturbed jaw function. ispartof: JOURNAL OF ORAL & FACIAL PAIN AND HEADACHE vol:33 issue:4 pages:389-398 ispartof: location:United States status: published

Background and aims Although literature concerning chronic pain patients indicates that cognitive behavioural variables, specifically acceptance and fear of movement/(re)injury, are related to life impact, the relative roles of these factors in relation to pain characteristics (e.g. intensity and spreading) and emotional distress are unclear. Moreover, how these variables affect rehabilitation outcomes in different subgroups is insufficiently understood. This study has two aims: (1) to investigate how pain, cognitive behavioural, and emotional distress variables intercorrelate and whether these variables can regress aspects of life impact and (2) to analyse whether these variables can be used to identify clinically meaningful subgroups at baseline and which subgroups benefit most from multimodal rehabilitation programs (MMRP) immediately after and at 12-month follow-up. Methods Pain aspects, background variables, psychological distress, cognitive behavioural variables, and two life impact variables were obtained from the Swedish Quality Registry for Pain Rehabilitation (SQRP) for chronic pain patients. These data were analysed mainly using advanced multivariate methods. Results The study includes 22,406 chronic pain patients. Many variables, including acceptance variables, showed important contributions to the variation in clinical presentations and in life impacts. Based on the statistically important variables considering the clinical presentation, three clusters/subgroups of patients were identified at baseline; from the worst clinical situation to the relatively good situation. These clusters showed significant differences in outcomes after participating in MMRP; the subgroup with the worst situation at baseline showed the most significant improvements. Conclusions Pain intensity/severity, emotional distress, acceptance, and life impacts were important for the clinical presentation and were used to identify three clusters with marked differences at baseline (i.e. before MMRP). Life impacts showed complex relationships with acceptance, pain intensity/severity, and emotional distress. The most significant improvements after MMRP were seen in the subgroup with the lowest level of functioning before treatment, indicating that patients with complex problems should be offered MMRP. Implications This study emphasizes the need to adopt a biopsychosocial perspective when assessing patients with chronic pain. Patients with chronic pain referred to specialist clinics are not homogenous in their clinical presentation. Instead we identified three distinct subgroups of patients. The outcomes of MMRP appears to be related to the clinical presentation. Thus, patients with the most severe clinical presentation show the most prominent improvements. However, even though this group of patients improve they still after MMRP show a complex situation and there is thus a need for optimizing the content of MMRP for these patients. The subgroup of patients with a relatively good situation with respect to pain, psychological distress, coping and life impact only showed minor improvements after MMRP. Hence, there is a need to develop other complex interventions for them.

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.

AIMS To investigate whether static jaw clenching can activate endogenous pain modulation and to compare the magnitude between healthy individuals and patients with temporomandibular disorder (TMD) myalgia. METHODS Thirty-three healthy volunteers (17 women and 16 men) and 20 women with TMD myalgia participated. Exercise-induced hypoalgesia (EIH) was examined by recording pressure pain thresholds (PPTs) in the masseter (MA) and brachioradialis (BR) muscles during tooth clenching until exhaustion. Pain and fatigue were assessed before and after clenching, and pain amplification was examined by applying a painful mechanical pressure at the MA for 2 minutes while assessing pain every 30 seconds. Analyses of data included repeated measures analysis of variance. RESULTS In the contracting MA, PPTs increased over time in all three groups (P < .001), while PPTs in the relaxed BR increased only in the men (P = .045). Pain intensity and fatigue in the MA increased after contraction in all groups (P < .003) and was higher in the women with TMD than in the healthy women (P < .001). Only the women with TMD showed pain amplification (P < .001). CONCLUSION Tooth clenching until exhaustion could activate EIH locally; ie, the magnitude of EIH in the MA was similar in women with TMD myalgia and pain-free women, indicating no deficient EIH in women with TMD. However, only women with TMD showed pain amplification during application of continuous painful pressure.

Characterized by chronic widespread pain, generalized hyperalgesia, and psychological stress, fibromyalgia (FM) is difficult to diagnose and lacks effective treatments. Endocannabinoids-arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), and the related oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA)-are endogenous lipid mediators with analgesic and anti-inflammatory characteristics, in company with psychological modulating properties (eg, stress and anxiety), and are included in a new emerging "ome," the endocannabinoidome. This case-control study compared the concentration differences of AEA, OEA, PEA, SEA, and 2-AG in 104 women with FM and 116 healthy control subjects. All participants rated their pain, anxiety, depression, and current health status. The relationships between the lipid concentrations and the clinical assessments were investigated using powerful multivariate data analysis and traditional bivariate statistics. The concentrations of OEA, PEA, SEA, and 2-AG were significantly higher in women with FM than in healthy control subjects; significance remained for OEA and SEA after controlling for body mass index and age. 2-AG correlated positively with FM duration and body mass index, and to some extent negatively with pain, anxiety, depression, and health status. In FM, AEA correlated positively with depression ratings. The elevated circulating levels of endocannabinoidome lipids suggest that these lipids play a role in the complex pathophysiology of FM and might be signs of ongoing low-grade inflammation in FM. Although the investigated lipids are significantly altered in FM, their biological roles are uncertain with respect to the clinical manifestations of FM. Thus plasma lipids alone are not good biomarkers for FM. PERSPECTIVE: This study reports about elevated plasma levels of endocannabinoidome lipid mediators in FM. The lipids' suitability to work as biomarkers for FM in the clinic were low; however, their altered levels indicate that a metabolic asymmetry is ongoing in FM, which could serve as a baseline during explorative FM pain management.

Background and objectives Non-specific low back pain (LBP) is responsible for triggering increased biomarkers levels. In this way, photobiomodulation therapy (PBMT) may be an interesting alternative to treat these patients. One of the possible biological mechanisms of PBMT involved to decrease pain intensity in patients with musculoskeletal disorders is modulation of the inflammatory mediators' levels. The aim of this study was to evaluate the effects of PBMT compared with placebo on inflammatory mediators' levels and pain intensity in patients with chronic non-specific LBP. Study design/materials and methods A prospectively registered, randomized triple-blinded (volunteers, therapists, and assessors), placebo-controlled trial was performed. Eighteen patients with chronic non-specific LBP were recruited and treated with a single session of active PBMT or placebo PBMT. The primary outcome of the study was serum prostaglandin E2 levels and the secondary outcomes were tumor necrosis factor-α, interleukin-6 levels, and pain intensity. All outcomes were measured before and after 15 minutes of treatment session. Results PBMT was able to decrease prostaglandin E2 levels at post-treatment compared with placebo, with a mean difference of -1470 pg/ml, 95% confidence interval -2906 to -33.67 in patients with LBP. There was no difference between groups in the other measured outcomes. Patients did not report any adverse events. Conclusion Our results suggest that PBMT was able to modulate prostaglandin E2 levels, indicating that this may be one of the mechanisms involved in the analgesic effects of PBMT in patients with LBP. Trial registration number (ClinicalTrials.gov): NCT03859505. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

The impact of comorbidities in fibromyalgia (FM) and temporomandibular disorders (TMD) have been well documented, but whether TMD sub-diagnoses myalgia (MYA) and myofascial pain with referral (MFP) differ regarding comorbidity is unclear. We aimed to elucidate this by studying the presence and associations of comorbidities in FM, MFP and MYA. An extended version of the Diagnostic Criteria for TMD axis II questionnaire was used to examine demographics, pain and comorbidities in 81 patients with FM, 80 with MYA, and 81 with MFP. Patients with MFP and FM reported a higher percentage of irritable bowel syndrome (IBS), depression, anxiety, somatic symptoms, perceived stress, and insomnia compared to MYA. Patients with FM had more IBS, depression, and somatic symptom disorder versus MFP. After adjusting for confounding variables, participants with anxiety, somatic symptoms disorder, pain catastrophizing, and perceived stress, as well as a greater number of comorbidities, were more likely to have MFP than MYA, whereas FM participants were more associated with IBS, somatic symptoms and insomnia compared to MFP. The number of comorbidities was significantly associated with widespread pain but not pain duration, body mass index or being on sick leave. In conclusion, patients with MFP were more similar to those with FM regarding comorbidity and should be differentiated from MYA in clinical settings and pain management.

AIMS To study the effect and cost-effectiveness of jaw exercise treatment in patients with masticatory myofascial pain. METHODS A total of 97 patients with myofascial pain according to the RDC/TMD were randomized into three groups: (1) jaw exercises; (2) stabilization appliance; or (3) no treatment. After 3 months, the patients were evaluated according to the following instruments: pain intensity according to a visual analog scale (VAS); global improvement according to the Patient Global Impression of Change scale (PGIC); depression and anxiety according to the Hospital Anxiety and Depression Scale (HADS); jaw function according to the Jaw Functional Limitation Scale (JFLS-20); consumption of analgesics; and frequency of tension-type headache. RESULTS Pain intensity during jaw movement decreased significantly more in the jaw exercise group compared to the no treatment group (P < .001). There was no statistically significant difference between the jaw exercise and stabilization appliance groups in this aspect. The patients in the treatment groups reported greater improvement on the PGIC compared to the no treatment group (P < .001). There was a significant decrease in headache frequency (P = .028), consumption of analgesics (P = .007), and JFLS scores (P = .008) in the jaw exercise group compared to the no treatment group. In the jaw exercise group, patients had fewer appointments and a lower mean treatment time compared to the group that received stabilization appliance treatment. CONCLUSION Jaw exercises are effective in reducing pain intensity, headache, and consumption of analgesics in patients with masticatory myofascial pain. Jaw exercises are also cost-effective when compared to treatment with a stabilization appliance.

The neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sex-related differences in its effect are not well understood in humans. Therefore, this longitudinal cohort study aimed to investigate the effect of NGF injection on density and expression of substance P, NMDA-receptor and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics, and to determine any possible sex-related differences in these effects of NGF. The magnitude of NGF-induced mechanical sensitization and pain during the oral function was significantly greater in women than in men (Ps=0.620,P=0.048), and expression of NMDA-receptors by putative nociceptors and change in temporal summation pain after glutamate injection (rs=0.561,P=0.003). In women, there was a significant inverse relationship between the degree of NGF-induced mechanical sensitization and the change in nerve fibers expression of NMDA-receptors alone (rs=-0.659,P=0.013), and in combination with NGF (rs=-0.764,P=0.001). In conclusion, women displayed a greater magnitude of NGF-induced mechanical sensitization, that also was associated with nerve fibers expression of NMDA-receptors, when compared to men. The present findings suggest that, in women, increased peripheral NMDA-receptor expression could be associated with masseter muscle pain sensitivity.

The aim of this study was to investigate if intramuscular injection of sterile water can be used as a human experimental pain model that resembles clinical craniofacial muscle pain and to analyse if the effects differ between sexes.This randomised, double-blind, placebo-controlled cross-over study included 30 healthy age-matched women and men (23.6 ± 2.4 years). At three sessions, with at least one week of washout in between, 0.2 mL of either sterile water (test-substance), hypertonic saline (58.5 mg/mL; active control) or isotonic saline (0.9 mg/mL; passive control) was randomly injected into the right masseter muscle. Pain intensity (VAS) was continuously assessed during 5 min whereafter pain duration (s) and pain area (au) were calculated; pressure pain thresholds (PPT;kPa) were recorded every 5 minutes during 30 minutes.Sterile water evoked pain of similar intensity (74.5 ± 49.9) as hypertonic saline (74.0 ± 50.5); whereas, isotonic saline evoked low-intensity pain (11.4 ± 23.4). The pain induced by sterile water and hypertonic saline had higher intensity (P 0.001), longer duration (P 0.001) and larger pain area (P 0.001) than isotonic saline. There were no significant differences in any pain variable between sterile water and hypertonic saline. The PPT did not change significantly after any substance, except for in women 5 minutes after sterile water injection (P 0.002). Pain duration was longer in the men for all substances (P 0.006), while the pain area was larger in women after injection of hypertonic saline (P 0.003).These results indicate that pain evoked by sterile water resembles clinical muscle pain and may offer a novel and simpler alternative to hypertonic saline injections.

Background: Glutamate, as well as nerve growth factor (NGF), is involved in nociception from peripheral tissues, such as muscles. However, the potential interaction between glutamate and NGF still remains unclear. This study investigated the interaction between glutamate-induced masseter muscle pain and NGF-induced allodynia on pain perception and jaw function in healthy individuals, and any possible sex differences in the response. Materials and Methods: Thirty pain-free adult participants (15 men and 15 women, mean age ± SD: 24 ± 4 years) participated in this study consisting of three sessions (Day 0, Day 3, and Day 4). NGF (5 μg/mL, 1.0 mL) was injected into the masseter muscle on Day 0 to induce muscle allodynia. On Day 3, glutamate (1M, 0.2 mL) was injected into the same masseter muscle. Before and after injections on Day 0 and 3, and post-injection (Day 4), spontaneous pain, temporal summation pain, as well as functional pain and fatigue in response to chewing were assessed with validated scales, and the pressure pain threshold (PPT) was recorded. Results: Spontaneous pain intensity was significantly higher after glutamate than NGF (P < 0.001). PPTs, temporal summation pain and functional measures were all reduced 3 days after NGF injection (P's < 0.001). Injection of glutamate on Day 3 did not further affect PPTs or temporal summation pain and there were no sex differences in the effects (P > 0.189). Chewing pain (P = 0.022) and fatigue increased after glutamate injection to a higher degree in the women than men (P = 0.037). Conclusion: Taken together, while glutamate injected into the NGF-sensitized muscle was painful, it did not alter muscle tenderness in women vs. men. However, pain and fatigue evoked by jaw function were higher in women after glutamate injection. This suggest that sex differences reported for masseter myalgia, mimicked by glutamate and NGF mediated pain in this study, may be greater for measures of perceived jaw function, which should be considered in a clinical evaluation.