Pain
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Genetic variation in melanocortin-1 receptor (MC1R) has a known role in red hair. Studies on responses to noxious stimuli in red-haired individuals have also been conducted, with mixed findings. To investigate a possible divergence between variants responsible for red hair and pain sensitivity, we performed a genewide association analysis in the Orofacial Pain: Prospective Evaluation and Risk Assessment cohort. ⋯ The 5'-UTR variant rs3212361 was further identified as an expression quantitative trait locus, associated with reduced transcript levels of MC1R in the brain and in the peripheral tibial nerve. Hair colour association analysis of the loss-of-function 5'-UTR rs3212361 allele identified association with red hair, and red hair colour itself was associated with a reduced count of persistent pain conditions. Together, our results suggest that primarily different mechanisms-affecting expression levels vs protein activity-mediated by different genetic variants in the MC1R locus contribute to red hair and pain.
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Pain disparities based on race, sex, age, and socioeconomic status have been well documented. This study aimed to examine interactions among these sociodemographic factors on self-reported bodily pain in an urban community sample to assess whether membership in multiple at-risk groups confers greater risk for pain independent of depressive symptomatology. Participants (N = 1173) were enrolled in the epidemiological Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, and reported experiences of pain in various body sites. ⋯ Among those above the poverty line, African American (AA) men were less likely to report pain than White men (P = 0.024) and AA women (P = 0.019), potentially due to greater stoicism or coping skills and sources of resilience. Consistent with prior research, significant main effects revealed that older age (OR = 2.16, 95% CI [1.28-3.64], P = 0.004) and higher depressive symptoms (OR = 1.03, 95% CI [1.02-1.04], P < 0.001) were associated independently with increased likelihood of reporting pain. This study demonstrates that in an urban population, intersecting sociodemographic factors create unique social identities that impact pain, and emphasizes the need for identification of relevant mediational pathways.
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Conventional magnetic resonance imaging of patients with trigeminal neuralgia (TN) does not typically reveal associated brain lesions. Here, we identify a unique group of TN patients who present with a single brainstem lesion, who do not fulfill diagnostic criteria for multiple sclerosis (MS). We aim to define this new clinical syndrome, which we term TN associated with solitary pontine lesion (SPL-TN), using a clinical and neuroimaging approach. ⋯ The lesions demonstrated abnormal white-matter microstructure, characterized by lower fractional anisotropy, and higher mean, radial, and axial diffusivities compared with the unaffected side. The brainstem trigeminal fiber microstructure within a lesion highlighted the difference between SPL-TN lesions and MS plaques. In conclusion, SPL-TN patients have identical clinical features to TN but have a single pontine lesion not in keeping with MS and are refractory to surgical management.
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Nonsteroidal anti-inflammatory drugs, commonly known as COX-1/COX-2 inhibitors, can be effective in treating mild to moderate migraine headache. However, neither the mechanism by which these drugs act in migraine is known, nor is the specific contribution of COX-1 vs COX-2. ⋯ Compared to vehicle (control group), celecoxib reduced CSD-induced dilatation of dural arteries and activation of dural and pial macrophages significantly, but not dilatation or constriction of pial arteries and veins, or the occurrence of plasma protein extravasation. Collectively, these findings suggest that a mechanism by which celecoxib-mediated COX-2 inhibition might ease the intensity of migraine headache and potentially terminate an attack is by attenuating dural macrophages' activation and arterial dilatation outside the blood-brain barrier, and pial macrophages' activation inside the blood-brain barrier.