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The associations between sleep disturbance, psychological dysfunction, pain intensity, and pain interference in children with chronic pain.

This study aimed to better understand the associations between both sleep disturbance and psychological dysfunction (i.e., anxiety and depressive symptoms, and anger), and pain intensity and pain interference, in a sample of children with chronic pain.

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Antibody-induced pain-like behavior and bone erosion: links to subclinical inflammation, osteoclast activity and ASIC3-dependent sensitization.

Several bone conditions e.g., bone cancer, osteoporosis and rheumatoid arthritis (RA) are associated with a risk of developing persistent pain. Increased osteoclast activity is often the hallmark of these bony pathologies and leads not only to bone remodeling but is also a source of pronociceptive factors that sensitize the bone-innervating nociceptors. Although historically bone loss in RA has been thought to be a consequence of inflammation, both bone erosion and pain can occur years before the symptom onset. Here we have addressed the disconnection between inflammation, pain and bone erosion by using a combination of two monoclonal antibodies isolated from B-cells of RA patients. We have found that mice injected with B02/B09 mAbs developed a long-lasting mechanical hypersensitivity which was accompanied by bone erosion in the absence of joint edema or synovitis. Intriguingly, we have noted a lack of analgesic effect of naproxen and a moderate elevation of few inflammatory factors in the ankle joints suggesting that B02/B09-induced pain-like behavior does not depend on inflammatory processes. In contrast, we found that inhibiting osteoclast activity and ASIC3 signaling prevented the development of B02/B09-mediated mechanical hypersensitivity. Moreover, we have identified phospholipase A2 (sPLA2) and lysophospatidylcholine 16:0 as critical components of B02/B09-induced pain-like behavior and shown that treatment with sPLA2 inhibitor reversed B02/B09-induced mechanical hypersensitivity and bone erosion. Taken together, our study suggests a potential link between bone erosion and pain in a state of subclinical inflammation and offers a step forward in understanding the mechanisms of bone pain in diseases like RA.

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A randomised placebo-controlled clinical trial on the efficacy of local lidocaine injections and oral citalopram for the treatment of complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a neuropathic pain condition with no universally recognised treatment. The study evaluates the efficacy of a therapeutic protocol consisting of oral citalopram and lidocaine injections in patients affected by CRPS.

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Involvement of bradykinin and bradykinin B1 receptor in patients with endometriosis.

Endometriosis (EM), a benign aseptic inflammatory disease, is associated with the presence of endometrial foci. Pain, one of its typical symptoms, has been reported as a constant stressor, but the etiology and pathogenesis of EM-associated pain are unclear. In the present study, eutopic and ectopic endometrium samples from women with EM (n=50) and normal endometrium samples from control subjects (n=20) were collected. Serum levels of prostaglandin E (PGE), prostaglandin F2α (PGF2α) and bradykinin (BK) were measured using commercial ELISA kits. The expression of the BKB1 receptor (BKB1R) protein was evaluated by immunohistochemical staining and western blot assay. The mRNA expression of BKB1R was measured by reverse transcription-quantitative PCR. The results revealed that there was a substantial increase in the protein and mRNA expression of BKB1R, as well as the release of PGE, PGF2α and BK in the blood, in the EM group compared with that in the control group. Moreover, PGE, PGF2α and BK levels were significantly correlated with each other, as well as with the pain intensity of EM. The increased expression levels of BKB1R protein and mRNA were positively correlated with the pain degree of EM. Thus, these data indicated that BK and BKB1R were involved in the pathological onset of EM-associated pain and that they may play an important role in EM-related pain by inducing PGE and PGF2α. The data indicate a potential new therapeutic target for EM-related pain.

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Frequent or chronic migraine negatively impacts personal, social and professional life.

INTRODUCTION Migraine affects 16% of the population and is a leading cause of disability. We aimed to describe the treatment status and impact of migraine in a selected cohort of patients with ≥ 4 migraine days per month. METHODS The study was conducted as a large, cross-sectional, multi-country online survey of adults (≥ 18 years) with migraine. Data presented here stem from 306 Danish respondents. Pre-specified quotas were applied so that 90% of respondents had used preventive migraine treatment and 80% had one or more treatment failures. RESULTS The median number of headache days per months was 11.3 (8-17.8) and 89 (29%) of patients met the criteria for chronic migraine. Most patients (n = 213; 70%) had taken preventive treatment (PT) for their migraines and among these 170 (80%) had experienced at least one treatment failure. Ninety-four (44.1%) patients reported being dissatisfied or mostly dissatisfied with their PTs. A negative impact of migraine on either private, social or professional life was reported by 303 (99.0%) patients; and among these, 195 (64.4%) reported an impact in all three domains. CONCLUSIONS Frequent or chronic migraine is associated with a considerable negative impact on personal, social and professional life. Treatment failure is frequent in this patient group, highlighting the need for continuous research and awareness of new treatment possibilities. FUNDING Novartis Pharmaceutical Corporation. TRIAL REGISTRATION not relevant.

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Efficacy and safety of EMA401 in peripheral neuropathic pain: results of 2 randomised, double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy.

The analgesic efficacy and safety of 2 phase 2b studies of EMA401 (a highly selective angiotensin II type 2 receptor antagonist) in patients with postherpetic neuralgia (EMPHENE) and painful diabetic neuropathy (EMPADINE) were reported. These were multicentre, randomised, double-blind treatment studies conducted in participants with postherpetic neuralgia or type I/II diabetes mellitus with painful distal symmetrical sensorimotor neuropathy. Participants were randomised 1:1:1 to either placebo, EMA401 25 mg, or 100 mg twice daily (b.i.d) in the EMPHENE and 1:1 to placebo or EMA401 100 mg b.i.d. in the EMPADINE. The primary outcome for both the studies was change in weekly mean of the 24-hour average pain score, using a numeric rating scale from baseline to week 12. Both the studies were prematurely terminated due to preclinical hepatotoxicity on long-term dosing, although not observed in these studies. Out of the planned participants, a total of 129/360 (EMPHENE) and 137/400 (EMPADINE) participants were enrolled. The least square mean reduction in numeric rating scale pain score was numerically in favour of EMA401 100 mg arm in both EMPHENE (treatment difference: -0.5 [95% confidence interval: -1.6 to 0.6; P value: 0.35]) and EMPADINE (treatment difference: -0.6 [95% confidence interval: -1.4 to 0.1; P value: 0.10]) at the end of week 12. However, as the studies were terminated prematurely, no firm conclusion could be drawn but the consistent clinical improvement in pain intensity reduction across these 2 studies in 2 different populations is worth noting.

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Can neuroimaging prove pain and suffering?: The influence of pain assessment techniques on legal judgments of physical versus emotional pain.

It is difficult to "prove" pain and suffering-particularly emotional suffering. Neuroimaging technology might bolster pain claims in civil cases by making pain seem less subjective. We examined how neuroimaging of physical and emotional pain influences judgments of pain and suffering across nonlegal and legal contexts.

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Predicting Clinical Improvement for Patients With Low Back Pain: Keeping It Simple for Patients Seeking Physical Therapy Care.

This study sought to develop and validate an original prediction formula that estimated the probability of success for patients with low back pain (LBP) to achieve a minimal clinically important difference (MCID) on the Modified Low Back Disability Questionnaire (MDQ).

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Pulsed Radiofrequency of the Occipital Nerves: Results of a Standardized Protocol on Chronic Headache Management.

Pulsed radiofrequency (PRF) of the occipital nerves has neuromodulative properties and is used for chronic pain management. However, its role in various types of chronic headaches has not been adequately investigated so far.

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Exercise combined with Acceptance and Commitment Therapy compared with a standalone supervised exercise programme for adults with chronic pain: a randomised controlled trial.

A prospective, 2-armed, parallel group randomised controlled trial (RCT) was conducted to compare the effectiveness of Acceptance and Commitment Therapy (ACT) combined with a supervised exercise programme with a supervised exercise programme alone for adults with chronic pain. One hundred seventy-five participants were individually randomised to receive either the combined Exercise and ACT (ExACT) intervention or supervised exercise alone. Those allocated to the ExACT group attended 8 weekly sessions with a psychologist based on the ACT approach, in addition to supervised exercise classes led by a physiotherapist. The control group attended weekly supervised exercise classes but did not take part in an ACT programme. Both groups were followed up postintervention and again after 12 weeks. The primary outcome was pain interference at 12-week follow-up. Estimates of treatment effects at follow-up were based on intention-to-treat analyses, implemented using a linear mixed-effects model. The findings of this RCT showed no difference in the effectiveness of ExACT, compared with a supervised exercise programme alone for the primary outcome pain interference at 12-week follow-up (mean difference -0.18, 95% confidence interval -0.84 to 0.48, P = 0.59, d = 0.11). ExACT group participants reported superior outcomes for pain self-efficacy, pain catastrophising, and committed action, compared with the control group, but there were no differences between the groups for other secondary outcomes or treatment process measures. Higher levels of treatment satisfaction and global impression of change were reported by ExACT group participants. Exercise combined with Acceptance and Commitment Therapy was not superior to a standalone supervised exercise programme for reducing pain interference in adults with chronic pain.

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