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Can a brief psychological expectancy intervention improve postoperative pain? A randomized, controlled trial in breast cancer patients.

Pain after surgery remains a major health problem, calling for optimized treatment regimens to maximize the efficacy of pharmacological interventions. In this randomized controlled trial, we tested in a routine surgical treatment setting whether postoperative pain can be reduced by a brief preoperative intervention, i.e., positive verbal suggestions in combination with sham acupuncture, designed to optimize treatment expectations. We hypothesized that the expectancy intervention as add-on to patient-controlled intravenous analgesia (PCIA) with morphine reduces patient-reported postoperative pain and improves satisfaction with analgesia.Ninety-six women undergoing breast cancer surgery were randomized at two stages: Prior to surgery, anesthesiologists delivered either positive or neutral verbal suggestions regarding the benefits of acupuncture needling on postoperative pain ("information condition"). Patients were then randomized to receive sham acupuncture or no sham-acupuncture during postoperative care ("sham acupuncture condition"). Average pain during the 24h observation period after surgery as primary and satisfaction with analgesia as secondary outcome were assessed with standardized measures, and analyzed with ANCOVA accounting for morphine dose, surgery-related and psychological parameters.Postoperative pain ratings were significantly reduced in patients who received positive treatment-related suggestions (F=4.45, p=0.038, main effect of information). Moreover, patients who received an intervention aimed at optimized treatment expectations reported significantly greater satisfaction with analgesia (F=4.89, p=0.030, interaction effect).Together, our proof-of-concept data support that optimizing treatment expectations via verbal suggestions may offer a promising approach to improve patient-reported outcomes. Future translational and clinical studies are needed to test such psychological strategies in different surgical interventions, patient groups, and pharmacological treatment regimens.

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Assessing evidence-based medicine and opioid/barbiturate as first-line acute treatment of pediatric migraine and primary headache: A retrospective observational study of health systems data.

To evaluate providers' use and predictors of evidence-based medicine or opioid/barbiturate as first-line acute treatment for children's initial presentation of acute migraine or primary headache.

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Non-invasive mechanical joint loading as an alternative model for osteoarthritic pain.

Mechanisms responsible for osteoarthritic pain remain poorly understood and current analgesic therapies are often insufficient. We have characterized and pharmacologically tested the pain phenotype of a non-invasive mechanical joint loading (MJL) model of osteoarthritis thus providing an alternative murine model for osteoarthritic pain.

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The Relationship Between β-Endorphin and Experimental Pain Sensitivity in Older Adults With Knee Osteoarthritis.

Osteoarthritis (OA) is the most common cause of pain in people aged >45 years, and the knee is the most commonly affected joint. There is a growing interest in understanding the biological factors that influence pain among older adults, but few studies have examined the relationship between β-endorphin and experimental pain sensitivity in older adults with knee OA pain. The purpose of this study was to investigate the relationship between resting plasma levels of β-endorphin and experimental pain sensitivity. This study was a secondary analysis of data for 40 adults with knee OA pain in whom quantitative sensory testing was used to measure experimental sensitivity to heat- and mechanically induced pain. The mean age of the sample was 60 years ( SD = 9 years), and approximately half were female (53%). Regression analyses indicated that β-endorphin level was negatively related to pressure pain threshold (β = -17.18, p = .02) and positively related to punctate mechanical pain (β = 17.13, p = .04), after controlling for age, gender, and OA severity. We did not find a significant relationship between β-endorphin and heat pain tolerance. The results suggest that higher circulating levels of β-endorphin at rest are associated with increased sensitivity to mechanical pain in older adults with knee OA. These findings add to the literature regarding biological factors associated with pain sensitivity in older adults with chronic pain. Additional studies are needed to identify mediators of the relationship between β-endorphin and pain sensitivity in OA and other musculoskeletal pain conditions.

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Pain in hypermobile Ehlers-Danlos syndrome: New insights using new criteria.

Features of the pain in hypermobile Ehlers-Danlos syndrome (hEDS) are complex and insufficiently known by clinicians. We enrolled 37 hEDS patients. Disease status was ascertained using revised 2017 International Classification criteria, in the EDS French National Reference Center. Patients were evaluated with a clinical examination, quantitative sensory testing, and validated questionnaires. Thirty-seven patients were evaluated. Pain had appeared at 10 ± 5 years old and became chronic at 20 ± 9 years old. hEDS was diagnosed at only 24 ± 10 years old. Ninety-seven percent of them had severe chronic pain, which gradually increased over time in 75% of them. The main location of pain was in joints and predominated in lower limbs. Patients with a generalized presentation of pain had older chronic pain and a higher impact on the affective component. Neuropathic pain was frequent in the most painful joint and associated with heat hypoesthesia. An asymmetric proprioception was found in one third of the patients. A very high rate of attempted suicide was observed. To conclude, pain in hEDS is severe, chronic, and disabling. Sensorial and proprioceptive sensibilities are also affected. Peripheral neuropathic pain is frequent and central sensitization appears to be a key step in the evolution of disease.

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Nerve growth factor gene therapy improves bone marrow sensory innervation and nociceptor-mediated stem cell release in a mouse model of type 1 diabetes with limb ischaemia.

Sensory neuropathy is common in people with diabetes; neuropathy can also affect the bone marrow of individuals with type 2 diabetes. However, no information exists on the state of bone marrow sensory innervation in type 1 diabetes. Sensory neurons are trophically dependent on nerve growth factor (NGF) for their survival. The aim of this investigation was twofold: (1) to determine if sensory neuropathy affects the bone marrow in a mouse model of type 1 diabetes, with consequences for stem cell liberation after tissue injury; and (2) to verify if a single systemic injection of the NGF gene exerts long-term beneficial effects on these phenomena.

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The Social and Functional Implications of High- Versus Low-Dose Opioids on Chronic Non-Cancer Pain.

Chronic non-cancer pain (CNCP) is a major health concern. Opioids may be a useful treatment option, but their use still remains controversial given the significant risks and epidemic of opioid addiction and abuse. There is limited data on whether opioid therapy is an effective treatment option for chronic non-cancer pain.

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Incident injury is strongly associated with subsequent incident temporomandibular disorder: Results from the OPPERA study.

Cross-sectional studies confirm, as expected, a positive association between jaw injury and painful temporomandibular disorders (TMDs), but prospective evaluations are lacking. We prospectively assessed incident jaw injury, injury type, and development of TMD in adults ages 18-44 years.Data were collected from 3,258 individuals from communities surrounding four U.S. academic institutes between 2006 and 2008. At enrollment, participants reported no TMD history and no facial injuries in the previous 6 months. Quarterly follow-up questionnaires assessed incident jaw injury, which was classified as intrinsic (attributed to yawning or prolonged mouth opening) or extrinsic (attributed to other causes). Examiners classified incident TMD during a median follow-up period of 2.8 years (range 0.2-5.2 years). Cox regression models used jaw injury as a time-dependent covariate to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with incident TMD.Among 1,729 participants with complete data, 175 developed TMD. Eighty percent of injuries were intrinsic. TMD annual incidence was nearly twice as high in those experiencing jaw injury (5.37%) compared to those who did not (3.44%). In the Cox model that accounted for timing of injury, the corresponding HR was 3.94 (95%CI=2.82-5.50) after adjusting for study site, age, race, and gender. Hazard ratios did not differ (p=0.91) for extrinsic injuries (HR=4.03, 95%CI=2.00-8.12) and intrinsic injuries (HR=3.85, 95%CI=2.70-5.49).Jaw injury was strongly associated with incident TMD. If surveillance and intervention following jaw injury is to be effective in preventing TMD, they should focus on both intrinsic and extrinsic injuries.

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N-3 fatty acids modulate repeated stress-evoked pain chronicity.

N-3 fatty acids, including docosahexaenoic acid (DHA), have a beneficial effect in both pain and psychiatric disorders. In fact, we previously reported that stress-induced pain prolongation might be mediated through the suppression of the G-protein coupled-receptor 40/free fatty acid receptor 1 (GPR40/FFAR1), which is activated by DHA and long-chain fatty acids. However, the involvement of GPR40/FFAR1 ligands in the development of stress-induced chronic pain has not yet been described. In this study, we investigated the role of DHA in stress-evoked pain chronicity using diet-induced n-3 fatty acid deficient mice. The n-3 fatty acid deficient mice showed exacerbation of anxiety-like behavior after repeated exposure to social defeat stress. The intact n-3 fatty acid deficient mice showed a decrease in paw threshold values. On the other hand, paw withdrawal thresholds of defeated but not non-stressed, n-3 fatty acid deficient mice continued until day 49 after paw surgery. We evaluated changes in phosphatidylcholine composition in the brains of repeat stress-evoked chronic pain model mice which were not on n-3 fatty acid deficiency diets On day 7 after paw surgery, phosphatidylcholines with DHA and other long-chain fatty acids were found to have decreased in the brains of stressed mice. Moreover, stress-induced persistent mechanical allodynia was improved by oral DHA supplementation. These results indicated that chronic stress may directly affect brain lipid composition; the related changes could be involved in chronic pain development. Our findings suggested that n-3 fatty acids, particularly DHA, are useful as a potential therapeutic target for stress-evoked chronic pain.

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Increased cerebral responses to salient transitions between alternating stimuli in chronic migraine with medication overuse headache and during migraine attacks.

In a previous study exploring central pain modulation with heterotopic stimuli in healthy volunteers, we found that transitions between sustained noxious and innocuous thermal stimulations on the foot activated the "salience matrix". Knowing that central sensory processing is abnormal in migraine, we searched in the present study for possible abnormalities of these salient transitional responses in different forms of migraine and at different time points of the migraine cycle.

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