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The contribution of patients’ presurgery perceptions of surgeon attributes to the experience of trust and pain during third molar surgery.

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Analgesic effect of perineural local anesthetics, steroids, and conventional medical management for trauma and compression-related peripheral neuropathic pain: a retrospective cohort study.

Trauma and compression are common causes of peripheral neuropathic pain (NP) refractory to conventional medical management (CMM). The role of perineural interventions in relieving this type of pain is unclear.

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Central Sensitization Phenotypes in Post Acute Sequelae of SARS-CoV-2 Infection (PASC): Defining the Post COVID Syndrome.

To develop and implement criteria for description of post COVID syndrome based on analysis of patients presenting for evaluation at Mayo Clinic Rochester between November 2019 and August 2020.

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Modified biofeedback (Conditioned Biofeedback) promotes anti-nociception by increasing the nociceptive flexion reflex threshold and reducing temporal summation of pain: A controlled trial.

This study examined whether a modified version of biofeedback (ie, Conditioned Biofeedback) that incorporated placebo analgesia-like manipulations could promote anti-nociception in healthy, pain-free participants. During Conditioned Biofeedback (n=28), sympathetic arousal level was displayed visually and participants were asked to reduce it while they received painful electric stimulations that were surreptitiously controlled by their arousal level. Thus, electric pain decreased as arousal decreased to associate successful arousal-reduction/relaxation with pain relief, and to promote expectations for future pain relief. A Biofeedback Only group (n=24) controlled for the general effects of biofeedback/relaxation. A Biofeedback+Shock group (n=21) controlled for the effects of practicing biofeedback during painful shocks. Nociceptive flexion reflex (NFR) threshold and temporal summation of pain (TS-pain) were used to assess changes in spinal nociception and pain facilitation, respectively. Results indicated all groups showed pre- to post-biofeedback increases in NFR threshold, but only the Conditioned Biofeedback group showed pre- to post-biofeedback reductions in TS-pain. Moreover, Conditioned Biofeedback resulted in a persistent (pre-biofeedback) increase in NFR threshold across sessions, whereas Biofeedback Only resulted in a persistent (pre-biofeedback) decrease in TS-pain. In sum, Conditioned Biofeedback may promote anti-nociception in healthy participants thus reducing risk for chronic pain. The study was registered prospectively on ClinicalTrials.gov (TU1560). PERSPECTIVE: A modified version of biofeedback that employs placebo analgesia manipulations was successful in increasing descending inhibition and reducing pain facilitation in healthy volunteers. As a result, it may be an effective means of reducing risk of future chronic pain onset by promoting an anti-nociceptive pain profile.

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Intra-epidermal nerve endings progress within keratinocyte cytoplasmic tunnels in normal human skin.

Intra-epidermal nerve endings, responsible for cutaneous perception of temperature, pain and itch, are conventionally described as passing freely between keratinocytes, from the basal to the granular layers of the epidermis. However, the recent discovery of keratinocyte contribution to cutaneous nociception implies that their anatomical relationships are much more intimate than what has been described so far. By studying human skin biopsies in confocal laser-scanning microscopy, we show that intra-epidermal nerve endings are not only closely apposed to keratinocytes, but can also be enwrapped by keratinocyte cytoplasms over their entire circumference and thus progress within keratinocyte tunnels. As keratinocytes must activate intra-epidermal nerve endings to transduce nociceptive information, these findings may help understanding the interactions between the keratinocytes and nervous system. The discovery of these nerve portions progressing in keratinocyte tunnels is a strong argument to consider that contacts between epidermal keratinocytes and intra-epidermal nerve endings are not incidental and argues for the existence of specific and rapid paracrine communication from keratinocytes to sensory neurons.

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Magnetic resonance imaging of neuroinflammation in chronic pain: a role for astrogliosis?

Non-invasive measures of neuroinflammatory processes in humans could substantially aid diagnosis and therapeutic development for many disorders, including chronic pain. Several proton Magnetic Resonance Spectroscopy (H-MRS) metabolites have been linked with glial activity (i.e. choline and myo-inositol) and found to be altered in chronic pain patients, but their role in the neuroinflammatory cascade is not well known. Our multimodal study evaluated resting fMRI connectivity and H-MRS metabolite concentration in insula cortex in 43 patients suffering from fibromyalgia, a chronic centralized pain disorder previously demonstrated to include a neuroinflammatory component, and 16 healthy controls. Patients demonstrated elevated choline (but not myo-inositol) in anterior insula (p=0.03), with greater choline levels linked with worse pain interference (r=0.41, p=0.01). In addition, reduced resting functional connectivity between anterior insula and putamen was associated with both pain interference (whole brain analysis, pcorrected<0.01) and elevated anterior insula choline (r=-0.37, p=0.03). In fact, anterior insula/putamen connectivity statistically mediated the link between anterior insula choline and pain interference (p<0.01), highlighting the pathway by which neuroinflammation can impact clinical pain dysfunction. In order to further elucidate the molecular substrates of the effects observed, we investigated how putative neuroinflammatory H-MRS metabolites are linked with ex-vivo tissue inflammatory markers in a nonhuman primate model of neuroinflammation. Results demonstrated that cortical choline levels were correlated with glial fibrillary acidic protein, a known marker for astrogliosis (Spearman r=0.49, p=0.03). Choline, a putative neuroinflammatory H-MRS assessed metabolite elevated in fibromyalgia and associated with pain interference, may be linked with astrogliosis in these patients.

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Higher burden of rare frameshift indels in genes related to synaptic transmission separate familial hemiplegic migraine from common types of migraine.

Familial hemiplegic migraine (FHM) is a rare form of migraine with aura that often has an autosomal dominant mode of inheritance. Rare mutations in the , and genes can all cause FHM revealing genetic heterogeneity in the disorder. Furthermore, only a small subset of the affected individuals has a causal mutation. We set out to investigate what differentiates patients with FHM with no mutation in any known FHM gene from patients with common types of migraine in both familial and sporadic cases.

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A cross-sectional survey of the perspectives of older people in the Scottish Highlands on the management of their chronic pain.

Although there is evidence of suboptimal outcomes in older people with chronic pain, little emphasis has been placed on those in remote and rural settings.

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Dysfunctional pain perception and modulation among torture survivors: The role of pain personification.

Individuals exposed to trauma, especially those who develop posttraumatic stress disorder (PTSD), are at a higher risk of suffering from chronic pain as well as altered pain perception and modulation. However, the underlying mechanisms of these processes are yet to be established. Recent findings have indicated that trauma survivors tend to personify chronic pain that is developed after the exposure, in a way that resonates with the traumatic experience. The aim of this study was to test whether pain personification plays a significant role in explaining the long-term links between trauma, PTSD and pain.

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Pre-consultation biopsychosocial data from patients admitted for management at pain centers in Norway.

Background and aims A bio-psycho-social approach has been recommended in multidisciplinary pain clinics, and in Norway patients with severe chronic nonmalignant pain (CNMP, defined as pain that has persisted for more than 3 months) might be treated at a regional multidisciplinary pain center. The specific aims of this study were (1) to describe characteristics of a sample of outpatients referred and accepted for treatment/management to three regional multidisciplinary pain centers in Norway, (2) to examine patient differences between the centers and (3) to study associations between symptom scores (insomnia, fatigue, depression, anxiety) and patient characteristics. Methods Patients, aged 17 years or older with CNMP admitted to and given a date for first consultation at one of three tertiary, multidisciplinary pain centers: St. Olavs Hospital Trondheim University Hospital (STO), Haukeland University Hospital (HUS) and University Hospital of North Norway (UNN), were included in the study. Data on demographics, physical activity, characteristics of pain, previous traumatic events, social network, Insomnia Severity Index (ISI), Chalder Fatigue Questionnaire (CFQ), Hopkins Symptom Checklist-25 (HSCL-25) and SF-36v2® were retrieved from the local quality registry at each pain center. Results Data from 1563 patients [mean age 42 (SD 15) years and 63% females] were available for analyses. Average years with pain were 9.3 (SD 9.1). Primary education as highest level of education was reported by 20%, being actively working/student/military by 32%, and no physical activity by 31%. Further, 48% reported widespread pain, 61% reported being exposed to serious life event(s), and 77% reported having a close friend to talk to. Non-worker status, no physical activity, lack of social network, reports of being exposed to serious life event(s) and widespread pain were all characteristics repeatedly associated with clinically high symptom scores. No significant differences between the centers were found in the proportions of patients reporting fatigue nor mean levels of insomnia symptoms. However, the proportion of patients reporting symptoms of anxiety and depression was a little lower at UNN compared with STO and HUS. Conclusions Analyses of registry data from three tertiary multidisciplinary pain centers in Norway support previous findings from other registry studies regarding patient characterized: A large proportion being women, many years of pain, low employment rate, low physical activity rate, and a large proportion reporting previous traumatic event(s). Characteristics such as non-work participation, no physical activity, lack of social network, have been exposed to serious life event(s), and chronic widespread pain were all associated with high clinical score levels of insomnia, fatigue, and mental distress. Health related quality of life was low compared to what has been reported for a general population and a range of other patient groups. Implications The findings of this study indicate that physical activity and work participation might be two important factors to address in the rehabilitation of patients with chronic non-malignant pain. Future studies should also explore whether pre consultation self-reported data might give direction to rehabilitation modalities.

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