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Concentration difficulties, forgetfulness and mental slowness are common in fibromyalgia syndrome (FMS); initial findings suggest that rheumatoid arthritis (RA) may also be accompanied by cognitive impairments. This study aimed to compare attentional performance between patients with FMS and RA. Attention was quantified in the domains of alerting, orienting and executive control using the Attentional Network Test-Interaction (ANT-I) in 56 women with FMS, 41 women with RA and 50 healthy women. Pain severity was statistically controlled in the group comparison. While FMS patients exhibited longer reaction times and made more errors on the ANT-I than RA patients and healthy women, performance did not differ between RA patients and healthy women. The magnitude of group differences did not vary by the experimental conditions of the ANT-I, suggesting a general attentional deficit in FMS rather than specific impairments in the domains of alerting, orienting and executive control. Differences between patient groups may relate to the different pathogenetic mechanisms involved in the disorders, i.e. inflammatory processes in RA and central nervous sensitization in FMS. In FMS, heightened activity in the pain neuromatrix may interfere with attention, because it requires enhanced neural resources in brain areas that are involved in both pain and attentional processing.
Despite epidurals being one of the most common interventional pain procedures for managing chronic spinal pain in the United States, expenditure analysis lacks assessment in correlation with utilization patterns.
A series of neuropathic pain conditions have a prevalence in older adults potentially associated with declined functioning of the peripheral and/or central nervous system. Neuropathic pain conditions demonstrate defective cortical excitability and intermissions, which raises questions of the impact of pain on cortical excitability changes and when to deliver repetitive transcranial magnetic stimulation (rTMS) to maximize the analgesic effects. Using prolonged continuous theta-burst stimulation (pcTBS), a relatively new rTMS protocol to increase excitability, this study was designed to investigate pcTBS analgesia and cortical excitability in the context of pain. With capsaicin application, twenty-nine healthy participants received pcTBS or Sham stimulation either in the phase of pain initialization (capsaicin applied) or pain ascending (20 min after capsaicin application). Pain intensity was measured with a visual-analogic scale (VAS). Cortical excitability was assessed by motor-evoked potential (MEP) and cortical silent period (CSP) which evaluates corticospinal excitability and GABAergic intracortical inhibition, respectively. Our data on pain dynamics demonstrated that pcTBS produced a consistent analgesic effect regardless of the time frame of pcTBS. More importantly, pcTBS delivered at pain initialization induced a larger pain reduction and a higher response rate compared to the stimulation during pain ascending. We further provide novel findings indicating distinct mechanisms of pcTBS analgesia dependent on the context of pain, in which pcTBS delivered at pain initialization was able to reverse depressed MEP, whereby pcTBS during pain ascending was associated with increased CSP. Overall, our data indicate pcTBS to be a potential protocol in pain management that could be delivered before the initialization of a pain episode to improve rTMS analgesia, potentially through inducing early corticospinal excitability changes that would be suppressed by nociceptive transmission.
Placebo and nocebo effects are positive and negative health outcomes that can be elicited by the psychosocial context. They can be mediated by expectations, and may emerge in somatic symptoms even when people are aware of these effects. Interindividual differences (e.g., in personality, affective states) could impact placebo and nocebo responding, but findings are inconsistent. The current work examined expectation as a mediator of the association between verbal placebo and nocebo suggestions (VSs) and histamine-induced itch across three experimental studies. Moreover, we examined whether interindividual differences (e.g., in optimism, neuroticism, behavioral activation system (BAS), body ignorance) modulated: (1) the direct association between VSs and itch (direct moderation), and (2) the indirect, expectation-mediated association between VSs and itch (moderated mediation). Positive VSs were compared to neutral instructions (Study 1; = 92) or negative VSs (Studies 2+3; = 203) in an open-label (i.e., explaining placebo and nocebo effects) or closed-label (concealed) context using PROCESS. First, mediation of VSs effects on itch by expectations was tested. Next, moderation by individual traits was explored using conditional process analyses. The effects of VSs on itch were significantly mediated by expectation in Study 1 and in the open-label (but not closed-label) contexts of Studies 2 and 3. Ignorance of bodily signals marginally moderated the direct effects of VSs on itch when closed-label suggestions were given: at low levels of body ignorance, effects of positive and negative VSs were stronger. Moreover, moderated mediation was observed in the open-label groups of Studies 2 and 3: The expectation-mediated effects of VSs on itch were stronger when BAS drive was lower. Overall, the effects of VSs on itch were mediated by expectations in the open-label, but not the closed-label context. Moreover, the current work suggests that placebo and nocebo effects may be moderated by ignorance of bodily signals and the BAS. There was limited evidence that other interindividual differences modulated placebo and nocebo responding in itch.
Previous studies targeting inter-individual differences in pain processing in migraine mainly focused on the perception of pain. Our main aim was to disentangle pain anticipation and perception using a classical fear conditioning task, and investigate how migraine frequency and pre-scan cortisol-to-dehydroepiandrosterone sulfate (DHEA-S) ratio as an index of neurobiological stress response would relate to neural activation in these two phases. Functional Magnetic Resonance Imaging (fMRI) data of 23 participants (18 females; mean age: 27.61± 5.36) with episodic migraine without aura were analysed. We found that migraine frequency was significantly associated with pain anticipation in brain regions comprising the midcingulate and caudate, whereas pre-scan cortisol-to DHEA-S ratio was related to pain perception in the pre-supplementary motor area (pre-SMA). Both results suggest exaggerated preparatory responses to pain or more general to stressors, which may contribute to the allostatic load caused by stressors and migraine attacks on the brain.
This study aimed to evaluate the prevalence of restless legs syndrome (RLS) in patients with migraine and explore its association with vitamin D deficiency, aiming to provide biological support for the comorbidity of migraine with RLS, and shed new lights into clinical diagnosis and treatment. A case-control study was performed on 175 migraine patients and 151 non-headache controls. The information of all subjects concerning headache severity [visual analog scale (VAS) score], RLS, RLS severity [International Restless Legs Scale (IRLS) score], sleep quality [Pittsburgh sleep quality index (PSQI)], anxiety and depression symptoms [hospital anxiety and depression scale (HADS)], and demographic data were collected. At the same time, serum 25-(OH) D levels were also measured (concentration <20 ng/ml was defined deficiency). Afterward, the logistic regression model was adopted to explore the risk factors for RLS in patients with migraines. Compared with control group, migraine group had lower vitamin D levels [(21.10 ± 6.58) vs. (16.42 ± 5.6) ng/ml, < 0.001], a higher rate of vitamin D deficiency (45.03 vs. 72%, <0001), higher prevalence of RLS (6.62 vs. 22.29%, < 0.001). Compared with the pure RLS group, RLS with the migraine group had lower vitamin D levels and higher IRLS score ( < 0.05). Compared with pure migraine group, migraine with RLS group had lower vitamin D levels [(17.36 ± 5.56) vs. (13.15 ± 4.42) ng/ml, < 0.001], higher incidence of vitamin D deficiency (66.18 vs. 92.31%, = 0.001), higher frequency of headache attacks ( = 0.004). Thereafter, the multivariate logistic regression model was employed to adjust confounding factors such as age, gender, season, frequency of headache attacks, PSQI score, and HADS scores. According to the results vitamin D deficiency in patients with migraines was an independent risk factor for RLS (OR = 5.03, 95%CI: 1.2-21.16, = 0.027). The prevalence of RLS in migraine patients was significantly higher than that in the non-headache population. Besides, vitamin D levels decreased, while the incidence of vitamin D deficiency increased in the migraine patients complicated with RLS. Finally, the occurrence of RLS in migraine patients was significantly related to vitamin D deficiency.
It is known that chronic pain makes it difficult to lose weight, but it is unknown whether obese patients (body mass index ≥30 kg/m) who experience significant pain relief after interdisciplinary multimodal pain rehabilitation (IMMPR) lose weight.
Calcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (K ) channels. Here, we investigated the effect of the K channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers.
Individuals with chronic pain often experience co-existing sleep problems and depression-related states. Chronic pain, sleep problems, and depression interrelate, and have been shown to exacerbate one another, which negatively impacts quality of life. This study explored the relationships between pain severity, pain interference, sleep quality, and depression among individuals with chronic pain. Secondly, we tested whether sleep quality may moderate the relationship between pain and depression. A cross-sectional survey was completed by 1,059 adults with non-malignant chronic pain conditions ( 43 years, 88% identified as women) and collected measures related to pain severity, pain interference, sleep quality, and depression. Multiple regression analyses found that pain severity, pain interference, and sleep quality are all significantly associated with depression. Secondly, moderated regression analyses revealed that sleep quality moderates the relationship between pain interference and depression among individuals with chronic pain such that good sleep quality attenuates the effect of pain interference on depression, and poor sleep quality amplifies the effect of pain interference on depression. These findings suggest that sleep quality may be a relevant therapeutic target for individuals with chronic pain and co-existing depression.
Pregabalin and gabapentin improve neuropathic pain symptoms but there are emerging concerns regarding their misuse. This is more pronounced among patients with substance use disorder, particularly involving opioids. Co-ingestion of gabapentinoids with opioids is increasingly identified in opioid related deaths, however, the molecular mechanism behind this is still unclear. We have sought to determine whether pregabalin or gabapentin directly modulates acute μ receptor signaling, or μ receptor activation by morphine.