Ventilator-induced Lung Injury Promotes Inflammation within the Pleural Cavity.

Mechanical ventilation contributes to the morbidity and mortality of patients in intensive care, likely through the exacerbation and dissemination of inflammation. Despite the proximity of the pleural cavity to the lungs and exposure to physical forces, little attention has been paid to its potential as an inflammatory source during ventilation. Here, we investigate the pleural cavity as a novel site of inflammation during ventilator-induced lung injury. Mice were subjected to low or high tidal volume ventilation strategies for up to 3 hours. Ventilation with a high tidal volume significantly increased cytokine and total protein levels in BAL and pleural lavage fluid. In contrast, acid aspiration, explored as an alternative model of injury, only promoted intraalveolar inflammation, with no effect on the pleural space. Resident pleural macrophages demonstrated enhanced activation after injurious ventilation, including upregulated ICAM-1 and IL-1ß expression, and the release of extracellular vesicles. In vivo ventilation and in vitro stretch of pleural mesothelial cells promoted ATP secretion, whereas purinergic receptor inhibition substantially attenuated extracellular vesicles and cytokine levels in the pleural space. Finally, labeled protein rapidly translocated from the pleural cavity into the circulation during high tidal volume ventilation, to a significantly greater extent than that of protein translocation from the alveolar space. Overall, we conclude that injurious ventilation induces pleural cavity inflammation mediated through purinergic pathway signaling and likely enhances the dissemination of mediators into the vasculature. This previously unidentified consequence of mechanical ventilation potentially implicates the pleural space as a focus of research and novel avenue for intervention in critical care.

Effectiveness of topical gabapentin in the treatment of vulvodynia: a narrative synthesis.

Vulvodynia is a leading cause of dyspareunia in premenopausal women, causing considerable morbidity and sexual dysfunction. A multimodal approach is used to treat vulvodynia. Alongside psychosocial interventions and physiotherapy, pharmacological treatment such as oral gabapentin are used in the treatment of vulvodynia. Topical formulations of gabapentin have shown promise in animal models and case reports investigating its use in other pain conditions. The topical route also avoids the systemic complications of gabapentin such as somnolence, dizziness, and peripheral edema. This study aimed to perform a narrative synthesis of studies investigating the use of topical gabapentin in the treatment of vulvodynia. The primary outcome was a change in pain score following treatment with topical gabapentin. A broad literature search was performed, which identified four studies for inclusion. The included studies reported improved pain measures following treatment; however, conclusions cannot be made due to methodological heterogeneity and inherent limitations. These include lack of control arms, small sample sizes, lack of patient randomization, and use of combination treatments. Due to the paucity of evidence, this review supports the future implementation of double-blind randomized controlled trials to further investigate the efficacy of topical gabapentin in the treatment of vulvodynia.