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CGRP and the Trigeminal System in Migraine.

The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene-related peptide (CGRP) within the context of the trigeminovascular system.

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The Effect of Patient Characteristics on Acupuncture Treatment Outcomes: An Individual Patient Data Meta-Analysis of 20,827 Chronic Pain Patients in Randomized Controlled Trials.

To optimally select chronic pain patients for different treatments, as it is of interest to identify patient characteristics that might moderate treatment effect. Our aim was to evaluate the impact of possible moderators on the effect of acupuncture treatment using a large data set.

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Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis.

Nerve growth factor (NGF) has emerged as a key driver of pain in osteoarthritis (OA) and antibodies to NGF are potent analgesics in human disease. Here, we validate a novel vaccine strategy to generate anti-NGF antibodies for reversal of pain behaviour in a surgical model of OA.

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Breakthrough cancer pain in patients with abdominal visceral cancer pain.

To assess the characteristics of breakthrough cancer pain (BTcP) in patients with abdominal cancer pain, and the eventual factors associated with its presentation.

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Metacognition across sensory modalities: Vision, warmth, and nociceptive pain.

The distinctive experience of pain, beyond mere processing of nociceptive inputs, is much debated in psychology and neuroscience. One aspect of perceptual experience is captured by metacognition-the ability to monitor and evaluate one's own mental processes. We investigated confidence in judgements about nociceptive pain (i.e. pain that arises from the activation of nociceptors by a noxious stimulus) to determine whether metacognitive processes contribute to the distinctiveness of the pain experience. Our participants made intensity judgements about noxious heat, innocuous warmth, and visual contrast (first-order, perceptual decisions) and rated their confidence in those judgements (second-order, metacognitive decisions). First-order task performance between modalities was balanced using adaptive staircase procedures. For each modality, we quantified metacognitive efficiency (meta-d'/d')-the degree to which participants' confidence reports were informed by the same evidence that contributed to their perceptual judgements-and metacognitive bias (mean confidence)-the participant's tendency to report higher or lower confidence overall. We found no overall differences in metacognitive efficiency or mean confidence between modalities. Mean confidence ratings were highly correlated between all three tasks, reflecting stable inter-individual variability in metacognitive bias. However, metacognitive efficiency for pain varied independently of metacognitive efficiency for warmth and visual perception. That is, those participants who had higher metacognitive efficiency in the visual task also tended to have higher metacognitive efficiency in the warmth task, but not necessarily in the pain task. We thus suggest that some distinctive and idiosyncratic aspects of the pain experience may stem from additional variability at a metacognitive level. We further speculate that this additional variability may arise from the affective or arousal aspects of pain.

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Pain and affective distress in arthritis: relationship to immunity and inflammation.

Most arthritides are associated with pain and psychological distress (clinically significant depression and anxiety). Pain and depression are mutually exacerbating; both may continue even when joint involvement appears well controlled. Area covered: There is strong evidence that arthritis-related stress impacts the central nervous system and, together with peripheral inflammatory changes, can cause central sensitization that can lead to chronic pain and worsening of affective distress. Cytokines and chemokines participate both in joint inflammation and in central sensitization. We review evidence of these relationships in five arthritides, namely rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, gout, and in osteoarthritis of the hips and knees. Central sensitization in these conditions results in long-lasting pain and psychological distress. Expert Commentary: Chronic pain and depression are important but often neglected in the clinical assessment and treatment of arthritis. The potential role of biologic cytokines and Janus kinase inhibitors in dealing with these symptoms needs further study.

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Gender Differences in the Association of Brain Gray Matter and Pain-Related Psychosocial Characteristics.

Although the association of gray matter morphology alterations and pain-related psychosocial characteristics with pain intensity and chronification in people with chronic spinal pain is evident, research on their mutual interaction is scarce and does not account for possible gender differences. Gender-based differences are, however, of utmost importance to consider when examining pain neurobiology.

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Trajectories of sickness absence and disability pension before and after opioid initiation for noncancer pain: a 10-year population-based study.

Chronic noncancer pain is a leading cause of sickness absence (SA) and disability pension (DP). The objectives of this study were to identify trajectories of SA/DP before and after strong and weak opioid initiation for noncancer pain and the factors associated with these trajectories. A longitudinal population-based study of 201,641 people (24-59 years) without cancer who initiated opioid analgesics in 2009 in Sweden was conducted. Trajectories of net annual SA/DP days in the 5 years before/after opioid initiation were estimated with group-based trajectory modelling. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with trajectory groups. Among the 6.9% of people initiating strong opioids, 12.5% had persistent high SA/DP (estimated 320 days/year) before and after opioid initiation and 72.9% had persistent low/minimum SA/DP (estimated 30 days/year). Approximately 8.6% of people had increasing SA/DP, and 6.1% had decreasing SA/DP after opioid initiation, although this seemed to reflect continuation of preinitiation patterns. Trajectories were similar at lower SA/DP days/year among those initiating weak opioids. Persistent high SA/DP among strong opioid initiators were associated with ≥5 comorbidities (OR = 8.72, 95% CI 5.61-13.56), ≤9 years of education (OR = 5.83, 95% CI 4.84-7.03), and previous use of antidepressants (OR = 4.57, 95% CI 3.89-5.37) and antipsychotics (OR = 4.49, 95% CI 2.93-6.88). Three-quarters of people initiating opioids for noncancer pain had persistent low/minimum levels of SA/DP 5 years before and after initiation. Increasing and decreasing SA/DP after opioid initiation seemed to reflect a continuation of preinitiation patterns. Our findings highlight the complex range of sociodemographic and medication-related factors associated with persistent SA/DP.

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Acute withdrawal and botulinum toxin A in chronic migraine with medication overuse: a double-blind randomized controlled trial.

Botulinum toxin A (BTA) is widely used as treatment of chronic migraine. Efficacy in studies, however, was only modest and likely influenced by unblinding due to BTA-induced removal of forehead wrinkles. Moreover, most study participants were overusing acute headache medications and might have benefitted from withdrawal. We assessed in a double blind, placebo-controlled, randomized clinical trial whether add-on therapy with BTA enhances efficacy of acute withdrawal. Participants were enrolled between December 2012 and February 2015, with follow-up to January 2016, in a single academic hospital in the Netherlands. A total of 179 participants, male and female, aged 18-65, diagnosed with chronic migraine and overuse of acute headache medication were included. All participants were instructed to withdraw acutely from all medication for a 12-week period, in an outpatient setting. In addition, they were randomly assigned (1:1) to 31 injections with BTA (155 units) or placebo (saline); to prevent unblinding, placebo-treated participants received low doses of BTA (17.5 units in total) in the forehead, along with saline injections outside the forehead region. Primary endpoint was percentage change in monthly headache days from baseline to the last 4 weeks of double-blind treatment (Weeks 9-12). Among 179 randomized patients, 90 received BTA and 89 received placebo, and 175 (98%) completed the double-blind phase. All 179 patients were included in the intention-to-treat analyses. BTA did not reduce monthly headache days versus placebo (-26.9% versus -20.5%; difference -6.4%; 95% confidence interval: -15.2 to 2.4; P = 0.15). Absolute changes in migraine days at 12 weeks for BTA versus placebo were -6.2 versus -7.0 (difference: 0.8; 95% confidence interval: -1.0 to 2.7; P = 0.38). Other secondary endpoints, including measures for disability and quality of life, did also not differ. Withdrawal was well tolerated and blinding was successful. Thus, in patients with chronic migraine and medication overuse, BTA does not afford any additional benefit over acute withdrawal alone. Acute withdrawal should be tried first before initiating more expensive treatment with BTA.

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Support for My Video is Support for Me: A YouTube Scoping Review of Videos Including Adolescents With Chronic Pain.

Adolescents are heavy users of social media as a venue to share experience and obtain information. Adolescents with chronic pain may be no different. Given that adolescents with chronic pain report feelings of social isolation, of being different, and lack peer understanding, social media may help them obtain social support. We conducted a scoping review of YouTube to identify how adolescents with chronic pain use this platform to connect with other adolescents.

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