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Structural and functional analyses of the human claustrum, a poorly understood telencephalic gray matter structure, are hampered by its sheet-like anatomical arrangement. Here, we first describe a functional magnetic resonance imaging (fMRI) method to reveal claustrum signal with no linear relationship with adjacent regions in human subjects. We applied this approach to resting state functional connectivity (RSFC) analysis of the claustrum at high resolution (1.5 mm isotropic voxels) using a 7T dataset (n = 20) and a separate 3T dataset for replication (n = 35). We then assessed claustrum activation during performance of a cognitive task, the multi-source interference task, at 3T (n = 33). Extensive functional connectivity was observed between claustrum and cortical regions associated with cognitive control, including anterior cingulate, prefrontal and parietal cortices. Cognitive task performance was associated with widespread activation and deactivation that overlapped with the cortical areas showing functional connectivity to the claustrum. Furthermore, during high cognitive conflict conditions of the task, the claustrum was significantly activated at the onset of the task, but not during the remainder of the difficult condition. Both of these findings suggest that the human claustrum can be functionally isolated with fMRI, and that it may play a role in cognitive control, and specifically task switching, independent of sensorimotor processing.
Recent studies suggested that epigenetic mechanisms, including DNA methylation, may be involved in migraine pathogenesis. The calcitonin gene-related peptide (CGRP), encoded by calcitonin gene-related peptide 1 gene, plays a key role in the disease. The aim of the study was to evaluate DNA methylation of gene in patients with episodic migraine. 22 patients with episodic migraine (F/M 15/7, mean age 39.7 ± 13.4 years) and 20 controls (F/M 12/8, mean age 40.5 ± 14.8 years) were recruited. Genomic DNA was extracted from peripheral blood. Cytosine-to-thymine conversion was obtained with sodium bisulfite. The methylation pattern of two CpG islands in the promoter region of gene was analyzed. No difference of methylation of the 30 CpG sites at the distal region of promoter was observed between migraineurs and controls. Interestingly, in patients with episodic migraine the methylation level was lower in 2 CpG sites at the proximal promoter region (CpG -1461, p = 0.037, and -1415, p = 0.035, respectively). Furthermore, DNA methylation level at different CpG sites correlates with several clinical characteristics of the disease, as age at onset, presence of nausea/vomiting, depression and anxiety (p < 0.05). In conclusion, we found that DNA methylation profile in two CpG sites at the proximal promoter region of is lower in migraineurs when compared to controls. Intriguingly, the -1415 hypomethylated unit is located at the CREB binding site, a nuclear transcription factor. In addition, we found a correlation between the level of methylation and several clinical features of migraine. Further studies with larger sample size are needed to confirm these results.
Numerous definitions of acute low back pain (aLBP) exist. The use of different definitions results in variability in reported prevalence or incidence, conflicting data regarding factors associated with the transition to chronic LBP (cLBP), and hampers comparability among studies.
Daily fluctuation in pain acceptance and its impact on the physical and psychosocial functioning of individuals living with spinal cord injury (SCI) and chronic pain has not been examined. We used end-of-day (EOD) diaries and multilevel mixed effects modeling (MLM) to examine the moderating effect of within- and between-person pain acceptance on associations between pain and physical and psychosocial functioning. Individuals with SCI and chronic pain (N = 124) completed seven days of EOD diaries, which included measures of pain acceptance, pain intensity, pain catastrophizing, pain interference, participation in social roles and activities (SRA), depressive symptoms, and positive affect and well-being (PAWB). We found within-person variability in pain acceptance (28% of the total variance) and a significant moderating effect of daily fluctuation in pain acceptance on the same-day pain intensity-SRA association. Within-person changes in pain acceptance were also associated with daily changes in pain interference, depressive symptoms, and PAWB, adjusting for pain intensity and catastrophizing. Findings highlight the potential for daily or momentary assessments of pain acceptance to enhance understanding of how psychological flexibility may contribute to pain-related outcomes. Future studies could further investigate stable and variable characteristics of pain acceptance and their individual contribution to physical and psychosocial functioning. PERSPECTIVE: Daily fluctuations in pain acceptance and their association with physical and psychosocial functioning were observed in the lives of individuals with spinal cord injury (SCI) and chronic pain. These findings may guide future studies to inform the development of effective, pain acceptance-focused individualized treatment approaches for chronic pain management in people with SCI.
The major dose-limiting toxicity of paclitaxel, one of the most commonly used drugs to treat breast cancer, is peripheral neuropathy (PIPN). PIPN, which persists into survivorship, has a negative impact on patient's mood, functional status, and quality of life. Currently, no interventions are available to treat PIPN. A critical barrier to the development of efficacious interventions is the lack of understanding of the mechanisms that underlie PIPN. While data from preclinical studies suggest that disrupting cytoskeleton- and axon morphology-related processes are a potential mechanism for PIPN, clinical evidence is limited. The purpose of the present study in breast cancer survivors was to evaluate whether differential gene expression and co-expression patterns in these pathways are associated with PIPN. Signaling pathways and gene co-expression modules associated with cytoskeleton and axon morphology were identified between survivors who received paclitaxel and did (n=25) or did not (n=25) develop PIPN. Pathway impact analysis identified four significantly perturbed cytoskeleton- and axon morphology-related signaling pathways. Weighted gene co-expression network analysis identified three co-expression modules. One module was associated with PIPN group membership. Functional analysis found that this module was associated with four signaling pathways and two ontology annotations related to cytoskeleton and axon morphology. This study, which is the first to apply systems biology approaches using circulating whole blood RNA-seq data in a sample of breast cancer survivors with and without chronic PIPN, provides molecular evidence that cytoskeleton- and axon morphology-related mechanisms identified in preclinical models of various types of neuropathic pain including chemotherapy-induced peripheral neuropathy, are found in breast cancer survivors and suggests pathways and a module of genes for validation and as potential therapeutic targets.
Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine.
To determine the relationship between hormonal contraceptive (HC) use and painful symptoms, particularly those associated with headache and painful temporomandibular disorders (TMD).
Knee pain in osteoarthritis is complex and complicated by the fact that osteoarthritis is considered to be a disorder of multiple phenotypes. This complexity challenges our understanding as to why some people remain relatively symptom-free, while others progress to persistent pain. One approach to understanding the mechanisms underlying the transition to persistent pain is by identifying pain susceptibility phenotypes in people with or at risk of knee osteoarthritis. Using variables representative of the multidimensional nature of pain in people who were free of persistent pain, we identified four phenotypes characterised by low pressure pain thresholds and temporal summation and not psychosocial factors in those who developed persistent pain two years later. The group with the highest proportion of low pressure pain thresholds and a moderate proportion with facilitated temporal summation had twice the odds of developing persistent knee pain. This work provides preliminary insights into the critical importance of altered neurobiological mechanisms of pain signalling that contributes to development of chronic, persistent pain in knee osteoarthritis.