Pain
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Chronic migraine (CM) is a disabling neurologic disorder that affects approximately 2% of the general population. Neuroimaging studies show functional involvement of trigeminal structures, such as the trigeminal spinal nucleus (Sp5) in migraine. However, structural changes in the Sp5 and the afferent trigeminal spinal tract (sp5) have never been found. ⋯ In addition, accompanying decreases in mean diffusivity, axial diffusivity, and radial diffusivity values were observed. This study shows that the sp5 undergoes neuroplastic changes, a feature which substantiates evidence for the hyperactivity of the Sp5 in patients with migraine. More insights are needed to observe whether these changes only occur in patients with CM.
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There is a need to better understand biological factors that increase the risk of persistent musculoskeletal (MSK) pain and heightened pain sensitivity. Knowing the heritability (how genes account for differences in people's traits) can enhance the understanding of genetic vs environmental influences of pain and pain sensitivity. However, there are gaps in current knowledge, including the need for intergenerational studies to broaden our understanding of the genetic basis of pain. ⋯ By contrast, heritability of cold pain sensitivity was not significant. This is the largest intergenerational study to date to comprehensively investigate the heritability of both MSK pain and pain sensitivity, using robust statistical analysis. This study provides support for the heritability of MSK pain and pain sensitivity to pressure, suggesting the need for further convergence of genetic and environmental factors in models for the development or maintenance of these pain disorders.
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Group I metabotropic glutamate receptors (group I mGluRs) have been implicated in several central nervous system diseases including chronic pain. It is known that activation of group I mGluRs results in the production of inositol triphosphate (IP3) and diacylglycerol that leads to activation of extracellular signal-regulated kinases (ERKs) and an increase in neuronal excitability, but how group I mGluRs mediate this process remains unclear. We previously reported that Orai1 is responsible for store-operated calcium entry and plays a key role in central sensitization. ⋯ Dihydroxyphenylglycine-induced activation of ERKs and modulation of neuronal excitability are abolished in cultured Orai1-deficient neurons. Moreover, DHPG-induced nociceptive behavior is markedly reduced in Orai1-deficient mice. Our findings reveal previously unknown functional coupling between Orai1 and group I mGluRs and shed light on the mechanism underlying group I mGluRs-mediated neuronal plasticity.