Presence of endometriosis and chronic overlapping pain conditions negatively impacts the pain experience in women with chronic pelvic-abdominal pain: A cross-sectional survey.

BACKGROUND: Evidence of overlap between endometriosis and chronic pain conditions is emerging; however, little is known about how the pain experience differs based on the presence or absence of endometriosis. OBJECTIVES: In a sample of women reporting chronic pelvic-abdominal pain (CPP), the aim of this study was to characterize differences in pain symptomatology between women with and without endometriosis and to examine the influence of chronic overlapping pain conditions (COPCs) on pain among these two groups. DESIGN: This was a cross-sectional study, based on an online survey. METHODS: Participants (aged 18+ years) completed a survey collecting pain diagnoses and symptoms assessing pelvic pain severity, pain interference, and pain impact. Independent sample t-tests, chi-square, and multiple linear regression models were employed to analyze group differences in pain symptomatology and COPCs. RESULTS: Of the 525 respondents with CPP, 25% (n = 133) reported having endometriosis. Women with endometriosis were younger at the onset of pelvic pain, relative to women without endometriosis (p = 0.04). There were no differences in age, race, ethnicity, or duration of pelvic pain between women with and without endometriosis. Women with endometriosis reported higher pelvic pain severity (+0.8, 95% CI = 0.4-1.1), pain interference (+5.9, 95% CI = 2.4-9.3), and pain impact (+1.9, 95% CI = 0.8-2.9). Endometriosis was associated with a higher number of COPCs (p = 0.003), with 25% (n = 33) of women reporting ⩾3 overlapping pain conditions compared with 12% (n = 45) of those without endometriosis. Women with endometriosis had a higher frequency of fibromyalgia (p < 0.001), chronic fatigue syndrome (p < 0.001), and temporomandibular disorder (p = 0.001). The number of COPCs was associated with higher pain severity, interference, and impact, independently of endometriosis. CONCLUSION: Women with endometriosis experienced higher levels of pain-related burden and COPCs compared with those without endometriosis. Pain intensity, interference, and impact increased with a higher number of pain conditions regardless of endometriosis presence.

Presence of endometriosis and chronic overlapping pain conditions negatively impacts the pain experience in women with chronic pelvic­abdominal pain: A cross-sectional surveyThe presence of endometriosis was associated with a higher number of chronic overlapping pain conditions (COPCs) and greater pain symptomatology, while a greater number of COPCs corresponded to increased pain burden among women with and without endometriosis. These findings underscore the need for a more comprehensive assessment of endometriosis that addresses the full experience of the disease, including its comorbidities. A greater characterization and measurement of COPCs has the potential to facilitate the development of tailored interventions for individuals with pain comorbidities, thereby contributing to improved clinical care strategies for endometriosis-related pain.

Megf10 deficiency impairs skeletal muscle stem cell migration and muscle regeneration.

Biallelic loss-of-function MEGF10 mutations lead to MEGF10 myopathy, also known as early onset myopathy with areflexia, respiratory distress, and dysphagia (EMARDD). MEGF10 is expressed in muscle satellite cells, but the contribution of satellite cell dysfunction to MEGF10 myopathy is unclear. Myofibers and satellite cells were isolated and examined from Megf10-/- and wild-type mice. A separate set of mice underwent repeated intramuscular barium chloride injections. Megf10-/- muscle satellite cells showed reduced proliferation and migration, while Megf10-/- mouse skeletal muscles showed impaired regeneration. Megf10 deficiency is associated with impaired muscle regeneration, due in part to defects in satellite cell function. Efforts to rescue Megf10 deficiency will have therapeutic implications for MEGF10 myopathy and other inherited muscle diseases involving impaired muscle regeneration.

Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions.

Mutations in MEGF10 cause early onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD), a rare congenital muscle disease, but the pathogenic mechanisms remain largely unknown. We demonstrate that short hairpin RNA (shRNA)-mediated knockdown of Megf10, as well as overexpression of the pathogenic human p.C774R mutation, leads to impaired proliferation and migration of C2C12 cells. Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration compared to myoblasts from wild type and mdx mice, whereas the dko mice show histological abnormalities that are not observed in either single mutant mouse. Cell proliferation and migration are known to be regulated by the Notch receptor, which plays an essential role in myogenesis. Reciprocal co-immunoprecipitation studies show that Megf10 and Notch1 interact via their respective intracellular domains. These interactions are impaired by the pathogenic p.C774R mutation. Megf10 regulation of myoblast function appears to be mediated at least in part via interactions with key components of the Notch signaling pathway, and defects in these interactions may contribute to the pathogenesis of EMARDD.