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Do chronic low back pain subgroups derived from dynamic quantitative sensory testing exhibit differing multidimensional profiles?

The relationship of pain sensitivity with pain and disability in low back pain (LBP) is complicated. It has been suggested increased understanding of dynamic quantitative sensory testing (QST) might be useful in increasing understanding of these relationships. This study aimed to create subgroups based on participant responses to dynamic QST, profile these subgroups based on multidimensional variables (including clinical measures of pain and disability, psychological and lifestyle variables and static QST), and investigate the association of subgroup membership with levels of pain intensity, LBP-related disability and disability risk at 12-month follow up.

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A Comparative Study of Fibromyalgia, Rheumatoid Arthritis, Spondyloarthritis, and Sjögren’s Syndrome; Impact of the Disease on Quality of Life, Psychological Adjustment, and Use of Coping Strategies.

Fibromyalgia, rheumatoid arthritis, spondyloarthritis, and Sjögren's syndrome are chronic rheumatic diseases with very different clinical characteristics, but which share symptoms such as pain and fatigue. The aim of the study was to examine the impact of the disease on psychological adaptation in fibromyalgia compared with other rheumatic diseases (rheumatoid arthritis, spondyloarthritis, and Sjögren's syndrome).

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Pain Prevalence, Chronicity and Impact within Subpopulations Based on Both Hispanic Ancestry and Race: United States, 2010-2017.

We provide national surveillance estimates of pain chronicity, severity and impact in adult subpopulations defined by both Hispanic Ancestry and Race. Data are from 144,434 adults who completed validated questionnaires in the 2010-2017 National Health Interview Survey asking about pain status within the last three (n=84,664) or six months (n=59,770). Multivariable logistic regression was used to assess the relationship between pain and ethnicity/race. Compared to White Puerto Rican participants, White participants with Central/South American and Mexican ancestry had reduced odds of reporting Category 3-4 pain and High-Impact Chronic Pain (HICP), while those of Cuban ancestry had reduced odds of only HICP – e.g., White participants with Mexican ancestry had 32% lower odds of having Category 3-4 pain and 50% lower odds of having HICP. While no differences were seen between White Puerto Rican and White Non-Hispanic participants for Category 3-4 pain, White Non-Hispanics had 40% lower odds of reporting HICP. Asian Non-Hispanic and Black Non-Hispanic participants had significantly lower odds of reporting Category 3-4 pain and HICP compared to White Puerto Rican participants, e.g., Black Non-Hispanic participants had 26% lower odds off having Category 3-4 pain and 42% lower odds of having HICP. Perspective: By examining pain status in discrete demographic groups based on Hispanic Ancestry and Race, this report further documents substantial differences in health status among underserved populations and provides a baseline for continuing surveillance research on pain, with the eventual goal of eliminating disparities in pain assessment and treatment.

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Prospective associations of frequent pain symptoms with suicidal behavior in adolescents.

Chronic pain and suicidal behavior are prevalent in adolescents. This longitudinal study examined the associations between pain symptoms and suicidal behavior in adolescents. A total of 7,072 adolescents participated in a follow-up study of behavior and health in Shandong, China. A self-administered structured questionnaire was used to assess pain symptoms (headache, stomachache, and other nonspecific pain), insomnia, anxiety/depression, substance use, stressful life events, prior suicidal behavior, and family environment in November-December in 2015. One year later, a follow-up survey was conducted. Mean age of the sample was 14.6 years, and half were female. Of the sample, 44.8% and 8.4% reported having one or more pain symptoms "sometimes" and "often", respectively. A total of 22.4% and 10.6% reported having lifetime suicidal behavior at baseline and subsequent suicidal behavior over the 1-year follow-up, respectively. Frequent pain was significantly associated with increased risk of suicidal behavior at baseline (OR=1.64, 95%CI=1.32-2.03) and during the subsequent year (OR=1.50, 95%CI=1.17-1.93) while adjusting for covariates. Among adolescents without a history of prior suicidal behavior, frequent pain was significantly associated with an approximately 70% increased risk of incident suicidal behavior (OR= 1.69, 95%CI=1.14-2.51). In conclusion, frequent pain appears to be predictive of adolescent suicidal behavior while adjusting for family and personal psychosocial covariates. PERSPECTIVE: This article presents the prospective associations of frequent pain symptoms with suicidal behavior in adolescents. Frequent pain was associated with a 50-70% increased risk of suicidal behavior 1 year later. The finding underscores the importance of pain assessment and treatment in comprehensive suicide prevention efforts in adolescents.

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Fibromyalgia Patients are not only Hypersensitive to Painful Stimuli but also to Sound Stimuli.

Fibromyalgia is a chronic widespread pain syndrome associated with hypersensitivity to nociceptive stimuli. This increased sensitivity of FM patients has been associated with central sensitization of dorsal horn neurons. Increasing evidence, however, suggests that the mechanisms of FM hypersensitivity not only affect pain but include light, smell, and sound. We hypothesized that supraspinal augmentation of sensory input including sound represent a hallmark of FM. We tested 23 FM patients and 28 healthy controls (HC) for sensory augmentation of nociceptive and non-nociceptive sensations: For assessment of nociceptive augmentation we used sensitivity adjusted mechanical and heat ramp & hold stimuli and for assessment of sound augmentation, we applied wideband noise stimuli using a random-staircase design. Quantitative sensory testing demonstrated increased heat and mechanical pain sensitivity in FM participants (p < .001). The sound pressures needed to report mild, moderate, and intense sound levels were significantly lower in FM compared to HC (p < .001), consistent with auditory augmentation. . FM patients are not only augmenting noxious sensations but also sound, suggesting that FM augmentation mechanisms are not only operant in the spinal cord but also in the brain. Whether the central nervous system mechanisms for auditory and nociceptive augmentation are similar, needs to be determined in future studies. PERSPECTIVE: This study presents QST evidence that the hypersensitivity of FM patients is not limited to painful stimuli but also to innocuous stimuli like sound. Our results suggest that brain mechanisms may be responsible for the increased sensitivity of FM patients.

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Pre-exposure, but not overshadowing, inhibits nocebo hyperalgesia.

Nocebo hyperalgesia is a pervasive problem that significantly adds to the burden of pain. Conditioning is a key mechanism of nocebo hyperalgesia and recent evidence indicates that, once established, nocebo hyperalgesia is resistant to extinction. This means that preventive strategies are critical. We therefore tested whether two novel strategies – overshadowing (Experiment 1) and pre-exposure (Experiment 2) – could inhibit conditioned nocebo hyperalgesia. Overshadowing involves introducing additional cues during conditioning that should compete with and overshadow learning about the target nocebo cue. Pre-exposure involves pre-exposing the target nocebo cue in the absence of pain, which should diminish its ability to become associated with pain later. In both studies, healthy volunteers (N=141) received exposure to a series of electrocutaneous pain stimuli with and without a sham electrode 'activated', which they were led to believe was a genuine hyperalgesic treatment. Nocebo conditioning was achieved by pairing sham activation with high pain prior to testing at equivalent pain intensity. In both studies, standard nocebo conditioning led to clear nocebo hyperalgesia relative to natural history controls. In Experiment 1, there was no evidence that overshadowing attenuated nocebo hyperalgesia. Importantly, however, Experiment 2 found that pre-exposure successfully attenuated nocebo hyperalgesia with post hoc analysis suggesting that this effect was dose-dependent. These findings provide novel evidence that pre-exposure, but not overshadowing, could be a cheap and effective way for mitigating the substantial harm caused by conditioned nocebo hyperalgesia in clinical settings. PERSPECTIVE: Nocebo hyperalgesia causes substantial patient burden with few preventive options available. Our study found novel evidence that pre-exposing treatment cues without pain, but not overshadowing them with other cues, has the capacity to inhibit conditioned nocebo hyperalgesia. Pre-exposure may therefore be an effective preventive strategy to combat nocebo hyperalgesia.

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Aberrant Brain Signal Variability and COMT Genotype in Chronic TMD Patients.

The analysis of brain signal variability is a promising approach to understand pathological brain function related to chronic pain. This study investigates whether blood-oxygen-level-dependent signal variability (BOLD) in specific frequency bands is altered in temporomandibular disorder (TMD) and correlated to its clinical features. Twelve patients with chronic myofascial TMD and 24 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. The BOLD was measured as the standard deviation of the BOLD time series at each voxel and compared between groups. We also examined the potential relationship between the BOLD and the catechol–methyltransferase () ValMet polymorphism. We assessed sensory-discriminative pain in the craniofacial region, pain sensitivity to sustained masseteric pain challenge, and TMD pain frequency for clinical correlation. Patients displayed reduced BOLD in the dorsolateral prefrontal cortex (dlPFC) as compared with HC in all frequency bands. In the slow-3 band, patients also showed reduced BOLD in the medial dorsal thalamus, primary motor cortex (M1), and primary somatosensory cortex (S1) and heightened BOLD in the temporal pole. Notably, we found a significant correlation between lower BOLD (slow-3) in the orofacial M1/S1 regions and higher clinical pain (intensity/area) and higher sensitivity of the masseter muscle pain. Moreover, lower BOLD (slow-3) in the dlPFC and ventrolateral PFC was associated with a higher TMD pain frequency. Participants who had the Met substitution exhibited lower BOLD in the dlPFC and higher BOLD in the temporal pole as compared with participants without the Met substitution. An increasing number of Met alleles was associated with lower dlPFC and greater temporal pole BOLD in both HC and TMD groups. Together, we demonstrated that chronic TMD patients exhibit aberrant BOLD in the top-down pain modulatory and sensorimotor circuits associated with their pain frequency and severity. ValMet polymorphism might affect clinical symptoms in association with regional brain signal variability, specifically involved in cognitive and emotional regulation of pain.

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Mambalgin-3 potentiates human acid-sensing ion channel 1b under mild to moderate acidosis: Implications as an analgesic lead.

Acid-sensing ion channels (ASICs) are expressed in the nervous system, activated by acidosis, and implicated in pain pathways. Mambalgins are peptide inhibitors of ASIC1 and analgesic in rodents via inhibition of centrally expressed ASIC1a and peripheral ASIC1b. This activity has generated interest in mambalgins as potential therapeutics. However, most mechanism and structure-activity relationship work on mambalgins has focused on ASIC1a, and neglected the peripheral analgesic target ASIC1b. Here, we compare mambalgin potency and mechanism of action at heterologously expressed rat and human ASIC1 variants. Unlike the nanomolar inhibition at ASIC1a and rodent ASIC1b, we find mambalgin-3 only weakly inhibits human ASIC1b and ASIC1b/3 under severe acidosis, but potentiates currents under mild/moderate acidosis. Our data highlight the importance of understanding the activity of potential ASIC-targeting pharmaceuticals at human channels.

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Integrated Meditation and Exercise Therapy: A Randomized Controlled Pilot of a Combined Nonpharmacological Intervention Focused on Reducing Disability and Pain in Patients with Chronic Low Back Pain.

This pilot trial examined the effects of a combined intervention of mindfulness meditation followed by aerobic walking exercise compared with a control condition in chronic low back pain patients. We hypothesized that meditation before exercise would reduce disability, pain, and anxiety by increasing mindfulness prior to physical activity compared with an audiobook control group.

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Mobile Neurofeedback for Pain Management in Veterans with TBI and PTSD.

Chronic pain is common in military veterans with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Neurofeedback, or electroencephalograph (EEG) biofeedback, has been associated with lower pain but requires frequent travel to a clinic. The current study examined feasibility and explored effectiveness of neurofeedback delivered with a portable EEG headset linked to an application on a mobile device.

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