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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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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Patellofemoral pain (PFP) is a common complaint among young sports active adolescents. This study evaluated the longitudinal changes in pronociceptive and antinociceptive mechanisms in young adolescents with PFP, their impact on prognosis, and responsiveness to treatment. Adolescents (N = 151, aged 10-14 years) diagnosed with PFP were compared with age-matched controls (N = 50) and subsequently tracked while participating in an intervention focussed on activity modification. ⋯ Pressure pain thresholds increased at both follow-ups (P < 0.001), and the increased PPTs were associated with decreases in pain intensity (r = 0.316; P < 0.001). Overall, TSP remained facilitated at follow-ups, and there was no change in CPM. This is the first study to demonstrate a pronociceptive mechanism as a prognostic factor in young adolescents with PFP.
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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.
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Group differences in touch and pain thresholds-and their neural correlates-were studied in women with provoked vestibulodynia (PVD; N = 15), a common subtype of vulvodynia (chronic vulvar pain), and pain-free control women (N = 15). Results from quantitative sensory testing and self-report measures indicated that, as compared with control participants, women with PVD exhibited allodynia (ie, pain in response to a normally nonpainful stimulus) and hyperalgesia (ie, an increased response to a normally painful stimulus) at vulvar and nonvulvar sites. In addition, brain imaging analyses demonstrated reduced difference scores between touch and pain in the S2 area in women with PVD compared with control participants, supporting previous findings of allodynia in women with PVD. ⋯ The results of this study contribute important information to the general pain and vulvodynia literatures in elucidating the specific sensorimotor neural mechanisms that underlie hyperalgesia in a chronic pain population. These results have implications for differentiating neural processing of touch and pain for women with and without PVD. Future research should attempt to examine alterations related to hyperalgesia in commonly comorbid conditions of PVD.