Pain
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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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Most centrally acting migraine preventive drugs suppress frequency and velocity of cortical spreading depression (CSD). The purpose of the current study was to determine how the new class of peripherally acting migraine preventive drug (ie, the anti-CGRP-mAbs) affect CSD-an established animal model of migraine aura, which affects about 1/3 of people with migraine-when allowed to cross the blood-brain barrier (BBB). ⋯ Similarly, we cannot conclude that CGRP is involved in the propagation velocity or the neuronal silencing period (also called cortical recovery period) that follows the CSD because similar effects were observed when the isotype was used. These finding call for caution with interpretations of studies that claim to show direct central nervous system effects of CGRP-mAbs.
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Painful distal symmetrical polyneuropathy is common in HIV and is associated with reduced quality of life. Research has not explored the experience of neuropathic pain in people with HIV from a person-centred perspective. Therefore, a qualitative interview study was conducted to more deeply understand the experience and impact of neuropathic pain in this population. ⋯ Theme 3 reflects the struggle for pain relief, including participants' attempts to "exhaust all options" and limited success in finding lasting relief. The final theme describes how pain management is complicated by living with HIV; this theme includes the influence of HIV stigma on pain communication and pain as an unwanted reminder of HIV. These data support the relevance of investigating and targeting psychosocial factors to manage neuropathic pain in HIV.
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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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Functional dyspepsia is a common functional gastrointestinal disorder. Gastric hypersensitivity (GHS) is a hallmark of this disorder, but the cellular mechanisms remain largely unknown. Stressors during gestational period could have effects on the offspring's tissue structure and function, which may predispose to gastrointestinal diseases. ⋯ A chromatin immunoprecipitation assay showed that PMS also enhanced the ability of NF-κBp65 to bind the promoter of Asic1 gene. Blockade of NF-κB using lentiviral-p65shRNA reversed upregulation of ASIC1 expression, GHS, and the hyperexcitability of DRG neurons. These data suggest that upregulation of ASIC1 expression is attributed to Asic1 promoter DNA demethylation and NF-κB activation, and that the enhanced interaction of the Asic1 and NF-κBp65 contributes to GHS induced by PMS.