Development of a computerized 2D rating scale for continuous and simultaneous evaluation of two dimensions of a sensory stimulus.

Introduction: One-dimensional rating scales are widely used in research and in the clinic to assess individuals' perceptions of sensory stimuli. Although these scales provide essential knowledge of stimulus perception, their limitation to one dimension hinders our understanding of complex stimuli. Methods: To allow improved investigation of complex stimuli, a two-dimensional scale based on the one-dimensional Gracely Box Scale was developed and tested in healthy participants on a visual and an auditory task (rating changes in brightness and size of circles and rating changes in frequency and sound pressure of sounds, which was compared to ratings on one-dimensional scales). Before performing these tasks, participants were familiarized with the intensity descriptors of the two-dimensional scale by completing two tasks. First, participants sorted the descriptors based on their judgment of the intensity of the descriptors. Second, participants evaluated the intensity of the descriptors by pressing a button for the duration they considered matching the intensity of the descriptors or squeezing a hand grip dynamometer as strong as they considered matching the intensity of the descriptors. Results: Results from these tasks confirmed the order of the descriptors as displayed on the original rating scale. Results from the visual and auditory tasks showed that participants were able to rate changes in the physical attributes of visual or auditory stimuli on the two-dimensional scale as accurately as on one-dimensional scales. Discussion: These results support the use of a two-dimensional scale to simultaneously report multiple dimensions of complex stimuli.

Cardiac-Gated Neuromodulation Increased Baroreflex Sensitivity and Reduced Pain Sensitivity in Female Fibromyalgia Patients.

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. A total of 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 min-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with two control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed. Reduced BRS in FM at baseline increased by 41% during two, ≈8 min-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps < 0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations (p < 0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic responses.

Predictors of Lumbar Spine Degeneration and Low Back Pain in the Community: The Johnston County Osteoarthritis Project.

OBJECTIVE: To determine the incidence and worsening of lumbar spine structure and low back pain (LBP) and whether they are predicted by demographic characteristics or clinical characteristics or appendicular joint osteoarthritis (OA). METHODS: Paired baseline (2003-2004) and follow-up (2006-2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for osteophytes (OST), disc space narrowing (DSN), spondylolisthesis, and presence of facet joint OA (FOA). Spine OA was defined as at least mild OST and mild DSN at the same level for any level of the lumbar spine. LBP, comorbidities, and back injury were self-reported. Weibull models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of spine phenotypes accounting for potential predictors including demographic characteristics, clinical characteristics, comorbidities, obesity, and appendicular OA. RESULTS: Obesity was a consistent and strong predictor of incidence of DSN (HR 1.80 [95% CI 1.09-2.98]), spine OA (HR 1.56 [95% CI 1.01-2.41]), FOA (HR 4.99 [95% CI 1.46-17.10]), spondylolisthesis (HR 1.87 [95% CI 1.02-3.43]), and LBP (HR 1.75 [95% CI 1.19-2.56]), and worsening of DSN (HR 1.51 [95% CI 1.09-2.09]) and LBP (HR 1.51 [95% CI 1.12-2.06]). Knee OA was a predictor of incident FOA (HR 4.18 [95% CI 1.44-12.2]). Spine OA (HR 1.80 [95% CI 1.24-2.63]) and OST (HR 1.85 [95% CI 1.02-3.36]) were predictors of incidence of LBP. Hip OA (HR 1.39 [95% CI 1.04-1.85]) and OST (HR 1.58 [95% CI 1.00-2.49]) were predictors of LBP worsening. CONCLUSION: Among the multiple predictors of spine phenotypes, obesity was a common predictor for both incidence and worsening of lumbar spine degeneration and LBP.

Different Phenotypes of Osteoarthritis in the Lumbar Spine Reflected by Demographic and Clinical Characteristics: The Johnston County Osteoarthritis Project.

OBJECTIVE: To determine if associations between demographic and clinical characteristics and appendicular joint osteoarthritis (OA) reflect different phenotypes of OA in the lumbar spine. METHODS: Participants were from the Johnston County OA Project. Demographic information consisted of age, sex, and race (white and African American), and clinical characteristics consisted of body mass index (BMI), low back pain and injury, and knee, hip, and hand OA. Participants were categorized as having spine OA, facet joint OA, both spine OA and facet joint OA, or neither spine OA nor facet joint OA (referent group). Multinomial regression models were used to determine odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Of 1,793 participants, the mean ± SD age was 66.2 ± 10.1 years, and the mean ± SD BMI was 30.7 ± 6.2. The majority of the participants were women (n = 1,144 [63.8%]), and 31.8% of the participants (n = 570) were African American. Eighteen percent of participants had neither spine OA nor facet joint OA, 22.8% had facet joint OA, 13.2% had spine OA, and 46.0% had both spine OA and facet joint OA. In adjusted analyses, African Americans were less likely to have facet joint OA (OR 0.68 [95% CI 0.49-0.95]) or both spine OA and facet joint OA (OR 0.51 [95% CI 0.37-0.70]). Women were more likely to have facet joint OA (OR 1.71 [95% CI 1.24-2.36]). Having a BMI of ≥30 was associated with having facet joint OA (OR 1.76 [95% CI 1.28-2.42]) and both spine OA and facet joint OA (OR 1.85 [95% CI 1.37-2.51]). Knee OA was associated with all 3 OA groups, while lower back injury was associated only with those with spine OA. Participants with hip OA were less likely to have facet joint OA. CONCLUSION: Race, sex, BMI, hip OA, and lower back injury may help identify different OA phenotypes in the lumbar spine.

Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.

Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Using logistic models adjusted for sex, age, enrollment site, and race, we identified 3 distinct loci that were significant in combined or sex-segregated analyses. A single-nucleotide polymorphism on chromosome 3 (rs13078961) was significantly associated with TMD in males only (odds ratio = 2.9, 95% confidence interval: 2.02-4.27, P = 2.2 × 10). This association was nominally replicated in a meta-analysis of 7 independent orofacial pain cohorts including 160,194 participants (odds ratio = 1.16, 95% confidence interval: 1.0-1.35, P = 2.3 × 10). Functional analysis in human dorsal root ganglia and blood indicated this variant is an expression quantitative trait locus, with the minor allele associated with decreased expression of the nearby muscle RAS oncogene homolog (MRAS) gene (beta = -0.51, P = 2.43 × 10). Male mice, but not female mice, with a null mutation of Mras displayed persistent mechanical allodynia in a model of inflammatory pain. Genetic and behavioral evidence support a novel mechanism by which genetically determined MRAS expression moderates the resiliency to chronic pain. This effect is male-specific and may contribute to the lower rates of painful TMD in men.

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain.

Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results. PERSPECTIVE: This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials.

Multimodal Vulvar and Peripheral Sensitivity Among Women With Vulvodynia: A Case-Control Study.

OBJECTIVE: To assess differences in vulvar and peripheral sensitivity between women with and without vulvodynia. METHODS: Women with vulvodynia (n = 41) and age-matched controls (n = 43) seen in the outpatient setting were evaluated via surveys, clinical examination, and multimodal sensory testing (pressure, heat, cold, vibration, and electrical stimulation). The relationships between sensitivity to various sensory modalities and case/control status, as well as by vulvodynia subgroups, were assessed using logistic regression. RESULTS: Women with vulvodynia were more sensitive to pressure and to electrical stimuli than were control women at the vulva (median, 22 vs 230 g and 0.495 vs 0.769 mA, respectively; P < 0.001 for each) and at the thumb (median, 2500 vs 4250 g and 0.578 vs 0.764 mA, respectively; P = 0.006 for pressure, P < 0.001 for electrical stimulation). Heat, cold, and vibration detection thresholds did not differ significantly between these groups (P > 0.025). Those reporting spontaneous pain versus provoked pain had greater pressure sensitivity to the thumb (median, 1850 vs 2690 g; P = 0.020) and greater electrical sensitivity at the introitus (0.450 vs 0.608 mA; P = 0.011), and those with primary versus secondary vulvodynia had substantially greater pressure sensitivity to the thumb (median, 2438 vs 3125 g, P = 0.004). However, having localized versus generalized vulvodynia was not associated with differences in pressure or electrical sensitivity. CONCLUSIONS: Sensitivities to pressure and electrical stimuli are greater among vulvodynia cases than among controls and support 2 previously defined subgroups-those reporting spontaneous pain versus those whose pain only occurred when provoked, and those with primary versus secondary vulvodynia.

A novel paradigm to evaluate conditioned pain modulation in fibromyalgia.

INTRODUCTION: Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus. METHODS: Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus. RESULTS: In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect (P>0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation (P=0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus (P=0.269). CONCLUSION: The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls.

Dorsal clitoral nerve injury following transobturator midurethral sling.

INTRODUCTION: Transobturator slings can be successfully used to treat stress urinary incontinence and improve quality of life through a minimally invasive vaginal approach. Persistent postoperative pain can occur and pose diagnostic and therapeutic dilemmas. Following a sling procedure, a patient complained of pinching clitoral and perineal pain. Her symptoms of localized clitoral pinching and pain became generalized over the ensuing years, eventually encompassing the entire left vulvovaginal region. AIM: The aim of this study was to highlight the clinical utility of conventional pain management techniques used for the evaluation and management of patients with postoperative pain following pelvic surgery. METHODS: We described a prototypical patient with persistent pain in and around the clitoral region complicating the clinical course of an otherwise successful sling procedure. We specifically discussed the utility of bedside sensory assessment techniques and selective nerve blocks in the evaluation and management of this prototypical patient. RESULTS: Neurosensory assessments and a selective nerve block enabled us to trace the source of the patient's pain to nerve entrapment along the dorsal nerve of the clitoris. We then utilized a nerve stimulator-guided hydrodissection technique to release the scar contracture. CONCLUSION: This case demonstrates that the dorsal nerve of the clitoris is vulnerable to injury directly and/or indirectly. Assimilation of a time-honored pain management construct for the evaluation and management of patients' pain may improve outcomes while obviating the need for invasive surgery.

Characterizing "fibrofog": Subjective appraisal, objective performance, and task-related brain activity during a working memory task.

The subjective experience of cognitive dysfunction ("fibrofog") is common in fibromyalgia. This study investigated the relation between subjective appraisal of cognitive function, objective cognitive task performance, and brain activity during a cognitive task using functional magnetic resonance imaging (fMRI). Sixteen fibromyalgia patients and 13 healthy pain-free controls completed a battery of questionnaires, including the Multiple Ability Self-Report Questionnaire (MASQ), a measure of self-perceived cognitive difficulties. Participants were evaluated for working memory performance using a modified N-back working memory task while undergoing Blood Oxygen Level Dependent (BOLD) fMRI measurements. Fibromyalgia patients and controls did not differ in working memory performance. Subjective appraisal of cognitive function was associated with better performance (accuracy) on the working memory task in healthy controls but not in fibromyalgia patients. In fibromyalgia patients, increased perceived cognitive difficulty was positively correlated with the severity of their symptoms. BOLD response during the working memory task did not differ between the groups. BOLD response correlated with task accuracy in control subjects but not in fibromyalgia patients. Increased subjective cognitive impairment correlated with decreased BOLD response in both groups but in different anatomic regions. In conclusion, "fibrofog" appears to be better characterized by subjective rather than objective impairment. Neurologic correlates of this subjective experience of impairment might be separate from those involved in the performance of cognitive tasks.

Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature.

Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and nonpainful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging "signature" cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of "central sensitivity syndromes" is based more soundly on clinical and epidemiological evidence. A coherent picture of a "central sensitization" mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence.

Programmed symptoms: disparate effects united by purpose.

Central sensitivity syndromes (CSS) share features of similar multiple symptoms, virtually unknown mechanisms and lack of effective treatments. The CSS nomenclature was chosen over alternatives because it focused on a putative physiological mechanism of central sensitization common to disorders such as fibromyalgia, irritable bowel syndrome, vulvodynia and temporomandibular disorder. Increasing evidence from multiple biological systems suggests a further development. In this new model central sensitization is part of a ensemble that includes also the symptoms of widespread pain, fatigue, unrefreshing sleep and dyscognition. The main feature is an intrinsic program that produces this ensemble to guide behavior to restore normal function in conditions that threaten survival. The well known "illness response" is a classic example that is triggered in response to the specific threat of viral infection. The major leap for this model in the context of CSS is that the symptom complex is not a reactive result of pathology, but a purposeful feeling state enlisted to combat pathology. Once triggered, this state is produced by potential mechanisms that likely include contributions of the peripheral and central immune systems, as well as stress response systems such as the autonomic system and the hypothalamic-pituitary-adrenal (HPA) axis. These act in concert to alter behavior in a beneficial direction. This concept explains similar symptoms for many triggering conditions, the poorly understood pathology, and the resistance to treatment.

Multidimensional Dyspnea Profile: an instrument for clinical and laboratory research.

There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence regarding its measurement properties and discuss its use and interpretation. The MDP assesses dyspnoea during a specific time or a particular activity (focus period) and is designed to examine individual items that are theoretically aligned with separate mechanisms. In contrast, other multidimensional dyspnoea scales assess recalled recent dyspnoea over a period of days using aggregate scores. Previous psychophysical and psychometric studies using the MDP show that: 1) subjects exposed to different laboratory stimuli could discriminate between air hunger and work/effort sensation, and found air hunger more unpleasant; 2) the MDP immediate unpleasantness scale (A1) was convergent with common dyspnoea scales; 3) in emergency department patients, two domains were distinguished (immediate perception, emotional response); 4) test-retest reliability over hours was high; 5) the instrument responded to opioid treatment of experimental dyspnoea and to clinical improvement; 6) convergent validity with common instruments was good; and 7) items responded differently from one another as predicted for multiple dimensions.

The relationship among psychological and psychophysiological characteristics of fibromyalgia patients.

UNLABELLED: This study examined the relationship of psychophysiological response patterns in fibromyalgia with psychological characteristics and comorbid mental disorders. Surface electromyographic data, systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels were recorded continuously during baseline, stress, and relaxation tasks. Cluster analysis revealed 4 subgroups of patients who differed on pain characteristics and cognitive, affective, and behavioral responses to pain and stress. The largest group (46.7%) was characterized by elevated blood pressure levels and stress reactivity (a disposition assumed to be a vulnerability factor for the development of diseases) associated with pain, anxiety, physical interference, low activity, and pain behaviors. A second group (41.6%) showed low baseline blood pressure and reactivity, and high activity and stress. A third group (9.2%) displayed high baseline skin conductance level, reactivity, and depression, and a fourth small group (2.5%) displayed elevated baseline electromyographic response and reactivity with high levels of anxiety and depression. These data suggest that unique psychophysiological response patterns are associated with psychological coping and mental disorders in fibromyalgia patients. The identification of the mechanisms that contribute to these group differences will further our understanding of the mechanisms involved in the development and maintenance of fibromyalgia and suggest differential treatment strategies. PERSPECTIVE: This article presents psychological characteristics and comorbidity with mental disorders of psychophysiological subgroups of fibromyalgia patients. This mechanistic analysis will assist scientific identification of systems-based pathways that contribute to autonomic and stress mechanisms that mediate chronic pain. Demonstration of distinct, homogeneous subgroups is an important step towards personalized, mechanism-oriented treatments.

Segregating the cerebral mechanisms of antidepressants and placebo in fibromyalgia.

UNLABELLED: Antidepressant drugs are commonly used to treat fibromyalgia, but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled clinical trial with milnacipran, a serotonin-norepinephrine reuptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus response assessments of pressure pain, measures of weekly pain, and fibromyalgia impact. Following treatment, milnacipran responders exhibited significantly higher activity in the posterior cingulum compared with placebo responders. The mere exposure to milnacipran did not explain our findings because milnacipran responders exhibited increased activity also in comparison to milnacipran nonresponders. Stimulus response assessments revealed specific antihyperalgesic effects in milnacipran responders, which was also correlated with reduced clinical pain and with increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing, an alteration implicated in fibromyalgia pathophysiology. PERSPECTIVE: This study presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo responders and milnacipran responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain.

Pressure pain thresholds fluctuate with, but do not usefully predict, the clinical course of painful temporomandibular disorder.

Central sensitization elicits pain hypersensitivity and is thought to be causally implicated in painful temporomandibular disorder (TMD). This causal inference is based on cross-sectional evidence that people with TMD have greater sensitivity than controls to noxious stimuli. We tested this inference in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study of 3258 adults with no lifetime history of TMD when enrolled (visit 1). During 5 years of follow-up, 1 group labeled "persistent TMD cases" (n=72) developed first-onset TMD by visit 2 that persisted ⩾ 6 months until visit 3. Another group labeled "transient TMD cases" (n=75) developed first-onset TMD at visit 2, which resolved by visit 3. Randomly sampled "controls" (n=126) remained TMD-free throughout all 3 visits. At each visit, pressure pain thresholds (PPTs) were measured by algometry at 10 cranial and bodily sites. In persistent TMD case patients, mean PPTs reduced 43 kPa (P<.0001) between visits 1 and 2 and thereafter did not change significantly. In transient TMD case patients, mean PPTs reduced 41 kPa (P<.001) between visits 1 and 2, and then increased 20 kPa (P<.001) by visit 3. These patterns were similar after excluding cranial sites symptomatic for TMD. Importantly, visit 1 PPTs had no clinically useful prognostic value in predicting first-onset TMD (odds ratio [OR]=1.07, P=.15). Among first-onset case patients, visit 2 PPTs were modest predictors of persistent TMD (OR=1.36, P=.002). In this longitudinal study, PPTs reduced when TMD developed then rebounded when TMD resolved. However, premorbid PPTs poorly predicted TMD incidence, countering the hypothesis that PPTs signify mechanisms causing first-onset TMD.

Associations between pressure-pain threshold, symptoms, and radiographic knee and hip osteoarthritis.

OBJECTIVE: To determine the association between generalized evoked pressure pain sensitivity with distal pressure-pain threshold (PPT) and the presence, severity, or number of involved knee/hip joints with radiographic osteoarthritis (rOA) or related symptoms. METHODS: Data for these cross-sectional analyses come from the second followup (2008-11) of the Johnston County Osteoarthritis Project (n = 1,602). PPT measurements were averaged over 2 trials from both the left and right trapezius. Outcomes of radiographic knee and hip OA were both defined by a Kellgren/Lawrence score of 2-4 and site-specific symptoms were ascertained at clinical interview. Associations were determined with multiple logistic regression models and two-way interactions were tested at P < 0.05. RESULTS: The sample was 67.2% women and 31.0% African American. Participants' mean ± SD age was 67.9 ± 9.0 years, mean ± SD body mass index was 31.5 ± 7.1 kg/m(2) , mean ± SD Center for Epidemiologic Studies Depression Scale score was 6.5 ± 7.4, and mean ± SD total PPT was 3.6 ± 0.7 kg. Significant associations were found between PPT and self-reported knee/hip symptoms. No significant associations were found between PPT and presence, severity, or number of joints with knee and hip rOA without accompanying symptoms. No significant interactions were found with demographic or clinical characteristics. CONCLUSION: PPT was significantly associated with self-reported single and multijoint symptoms. In contrast, after adjustment, PPT measured at the trapezius was not associated with asymptomatic knee or hip rOA. As such, PPT may prove to be a useful indicator of rOA pain processing and of why individuals respond favorably and others do not to treatments targeting rOA.

Immune and endocrine function in patients with burning mouth syndrome.

OBJECTIVES: Research suggests that varied etiologic factors are responsible for burning mouth syndrome (BMS). We examined the role of immune and endocrine function in the pathology of BMS. METHODS: We conducted a case-control study to evaluate immune (lymphocyte subpopulations) and endocrine (hypothalamus-pituitary-adrenal axis and sympathetic-adrenomedullary system) function in 47 female BMS patients and 47 age-matched female controls presenting at an university clinic. Psychological state was assessed with the Zung Self-Rating Depression Scale and Taylor Manifest Anxiety Scale. RESULTS: BMS patients were significantly more anxious than controls (P=0.011). Plasma adrenaline level was significantly lower (P=0.020) in BMS patients than in controls, and linear regression analysis of all patients combined revealed that depression level was significantly positively associated with plasma noradrenaline and cortisol levels (P=0.002 and 0.001, respectively). However, as compared with controls, BMS patients had a significantly lower CD8(+) cell count (P<0.001) and a significantly higher CD4/CD8 ratio (P=0.002). Discriminant analysis revealed that CD8(+) cell count and CD4/CD8 ratio were independent variables that distinguished BMS patients from controls. DISCUSSION: The immunoendocrine system is substantially involved, and may have a key role, in the mechanism of chronic pain in BMS patients. Immune function was significantly and specifically suppressed in BMS, although the hypothalamic-pituitary-adrenal axis and sympathetic nervous system were predominantly activated by psychological stress that was not specific to BMS.