Accepted

This study sought to describe migrainous headache frequency and severity and to examine the relationship between trauma, discrimination, and migraine-associated disability in a sample of sexual and/or gender minority (SGM) adults.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease with a variety of symptoms such as post-exertional malaise, fatigue, and pain, but where aetiology and pathogenesis are unknown. An increasing number of studies have implicated the involvement of the immune system in ME/CFS. Furthermore, a hereditary component is suggested by the reported increased risk for disease in relatives, and genetic association studies are being performed to identify potential risk variants. We recently reported an association with the immunologically important human leucocyte antigen (HLA) genes HLA-C and HLA-DQB1 in ME/CFS. Furthermore, a genome-wide genetic association study in 42 ME/CFS patients reported significant association signals with two variants in the T cell receptor alpha (TRA) locus (P value <5 × 10). As the T cell receptors interact with the HLA molecules, we aimed to replicate the previously reported findings in the TRA locus using a large Norwegian ME/CFS cohort (409 cases and 810 controls) and data from the UK biobank (2105 cases and 4786 controls). We investigated numerous SNPs in the TRA locus, including the two previously ME/CFS-associated variants, rs11157573 and rs17255510. No associations were observed in the Norwegian cohort, and there was no significant association with the two previously reported SNPs in any of the cohorts. However, other SNPs showed signs of association (P value <0.05) in the UK Biobank cohort and meta-analyses of Norwegian and UK biobank cohorts, but none survived correction for multiple testing. Hence, our research did not identify any reliable associations with variants in the TRA locus.

Pain is the main symptom of entheseal diseases (enthesopathies) despite a paucity of nerve endings in the enthesis itself. Eicosanoids, cytokines, and neuropeptides released during inflammatory and repeated non-physiological mechanical challenge not only stimulate or sensitize primary afferent neurons present in structures adjacent to the enthesis or but also trigger a "neuro-vascular invasion" that allows spreading of nerves and blood vessels into the enthesis. Nociceptive pseudo-unipolar neurons support this process by releasing neurotransmitters from peripheral endings that induce neovascularization and peripheral pain sensitization. This process may explain the frequently observed dissociation between subjective symptoms, i.e. pain and the structural findings in imaging in entheseal disease.

Chronic vulvar pain (CVP) is pain in the vulvar area exceeding three months of duration. Previous studies have reported a prevalence of 7-8% in the general population and observed an association between CVP and other chronic pain, affective disorders and early life stressors. The aim of this study was to estimate the prevalence of CVP among gynecological outpatients and to explore its association with child sexual abuse, comorbid fibromyalgia and mental health.

The neurotrophin brain-derived neurotrophic factor (BDNF), which acts as a transducer, is responsible for improving cerebral stroke, neuropathic pain, and depression. Exercise can alter extracellular nucleotide levels and purinergic receptors in central nervous system (CNS) structures. This inevitably activates or inhibits the expression of BDNF via purinergic receptors, particularly the P2X receptor (P2XR), to alleviate pathological progression. In addition, the significant involvement of sensitive P2X4R in mediating increased BDNF and p38-MAPK for intracerebral hemorrhage and pain hypersensitivity has been reported. Moreover, archetypal P2X7R blockade induces mouse antidepressant-like behavior and analgesia by BDNF release. This review summarizes BDNF-mediated neural effects via purinergic receptors, speculates that P2X4R and P2X7R could be priming molecules in exercise-mediated changes in BDNF, and provides strategies for the protective mechanism of exercise in neurogenic disease.