Rejected

To review the best pharmacologic and nonpharmacologic interventions in the management of chronic pain in elderly patients with depression.

We have recently demonstrated that endometrial-myometrial interface (EMI) disruption (EMID) can cause adenomyosis in mice, providing experimental evidence for the well-documented epidemiological finding that iatrogenic uterine procedures increase the risk of adenomyosis. To further elucidate its underlying mechanisms, we designed this study to test the hypothesis that Schwann cells (SCs) dedifferentiating after EMID facilitate the genesis of adenomyosis, but the suppression of SC dedifferentiation perioperatively reduces the risk. We treated mice perioperatively with either mitogen-activated protein kinase kinase (MEK)/extracellular-signal regulated protein kinase (ERK) or c-Jun N-terminal kinase (JNK) inhibitors or a vehicle 4 h before and 24 h, 48 h and 72 h after the EMID procedure. We found that EMID resulted in progressive SCs dedifferentiation, concomitant with an increased abundance of epithelial cells in the myometrium and a subsequent epithelial-mesenchymal transition (EMT). This EMID-induced change was abrogated significantly with perioperative administration of JNK or MEK/ERK inhibitors. Consistently, perioperative administration of a JNK or a MEK/ERK inhibitor reduced the incidence by nearly 33.5% and 14.3%, respectively, in conjunction with reduced myometrial infiltration of adenomyosis and alleviation of adenomyosis-associated hyperalgesia. Both treatments significantly decelerated the establishment of adenomyosis and progression of EMT, fibroblast-to-myofibroblast trans-differentiation and fibrogenesis in adenomyotic lesions. Thus, we provide the first piece of evidence strongly implicating the involvement of SCs in the pathogenesis of adenomyosis induced by EMID.

Pain assessment is essential for preclinical and clinical studies on pain. The mouse grimace scale (MGS), consisting of five grimace action units, is a reliable measurement of spontaneous pain in mice. However, MGS scoring is labor-intensive and time-consuming. Deep learning can be applied for the automatic assessment of spontaneous pain. We developed a deep learning model, the DeepMGS, that automatically crops mouse face images, predicts action unit scores and total scores on the MGS, and finally infers whether pain exists. We then compared the performance of DeepMGS with that of experienced and apprentice human scorers. The DeepMGS achieved an accuracy of 70-90% in identifying the five action units of the MGS, and its performance (correlation coefficient = 0.83) highly correlated with that of an experienced human scorer in total MGS scores. In classifying pain and no pain conditions, the DeepMGS is comparable to the experienced human scorer and superior to the apprentice human scorers. Heatmaps generated by gradient-weighted class activation mapping indicate that the DeepMGS accurately focuses on MGS-relevant areas in mouse face images. These findings support that the DeepMGS can be applied for quantifying spontaneous pain in mice, implying its potential application for predicting other painful conditions from facial images.

SARS-CoV virus infection results in a dysbalanced and severe inflammatory response with hypercytokinemia and immunodepression. Viral infection triggers systemic inflammation and the virus itself can potentially cause vascular damage, including blood-brain barrier (BBB) disruption and alterations in the coagulation system, which may result in cardiovascular and neurovascular events. Here, we review the literature and present a case of COVID-19 infection leading to an aneurysmal subarachnoid haemorrhage (aSAH).

, a traditional medicinal plant, is extensively used for treating various painful conditions, such as nose bleeds, wounds, and sinusitis. A phytochemical investigation of the chloroform fraction of led to the isolation of salicylalazine. Salicylalazine was assessed in vivo for analgesia, muscle relaxation, sedative, and anti-inflammatory properties, as well as in vitro for COX-1/2 inhibition activities. It was assessed against a hot plate-induced model at different doses. The muscle relaxant potential of salicylalazine was evaluated in traction and inclined screening models, while sedative properties were determined using an open-field model. The anti-inflammatory potential of salicylalazine was assessed in histamine and carrageenan-induced paw edema screening models. Salicylalazine exhibited significant analgesic potential in a dose-dependent manner. In both screening models, an excellent time-dependent muscle-relaxation effect was observed. Salicylalazine demonstrated excellent sedation at high doses. Its anti-inflammatory activity was determined through the initial and late phases of edema. It exhibited anticancer potential against NCI-H226, HepG2, A498, and MDR2780AD cell lines. In vitro, salicylalazine showed preferential COX-2 inhibition (over COX-1) with an SI value of 4.85. It was less effective in the initial phase, while, in the later phase, it demonstrated significant effects at 15 and 20 mg/kg doses compared with the negative control. Salicylalazine did not exhibit cytotoxicity in the MTT assay, preliminarily indicating its safety.

Trigeminal neuralgia is unilateral, lancinating, episodic pain that can be provoked by routine activities. Anticonvulsants, such as carbamazepine, are the drugs of choice; however, these possess side-effects. Microvascular decompression is the most effective surgical technique with a higher success rate, although occasionally causes adverse effects. The potential treatment for this type of pain remains unmet. Increased tetrahydrobiopterin (BH4) levels have been reported in association with axonal injury. This study aimed to evaluate the effect of tranilast on relieving neuropathic pain in animal models and analyze the changes in BH4 synthesis. Neuropathic pain was induced via infraorbital nerve constriction. Tranilast, carbamazepine, or saline was injected intraperitoneally to assess the rat's post-intervention pain response. In the von Frey's test, the tranilast and carbamazepine groups showed significant changes in the head withdrawal threshold in the ipsilateral whisker pad area. The motor coordination test showed no changes in the tranilast group, whereas the carbamazepine group showed decreased performance, indicating impaired motor coordination. Trigeminal ganglion tissues were used for the PCR array analysis of genes that regulate the BH4 pathway. Downregulation of the sepiapterin reductase () and aldoketo reductase () genes after tranilast injection was observed compared to the pain model. These findings suggest that tranilast effectively treats neuropathic pain.

The COVID-19 (coronavirus disease 2019) affected individuals and society and caused disruption, anxiety, stress, and loneliness. Being hospitalized during the pandemic increase a patient's negative feelings. This study aimed to evaluate the impact of the COVID-19 pandemic on patients' feelings (loneliness, depression, hope, self-efficacy) during a hospital stay. This study included 207 women, aged from 15 to 83 years (55 ± 21.2) that were hospitalized during the pandemic in Białystok, Łomża, and Biała Podlaska, Poland at internal medicine departments. The main reasons for hospitalization were cardiovascular diseases, abdominal pain, chronic obstructive pulmonary disease, pneumonia, diabetes, and unknown fever. Respondents were asked to complete the following questionnaires: Sense of Loneliness (the DJGLS), Depression Beck Inventory (BDI), Basic Hope (BHI-12), and Self-Efficacy (GSES). Most of the studied group of women had an average sense of loneliness. A greater sense of loneliness was found among hospitalized women living in the countryside-the lowest sense of loneliness and depression was among women with higher education and the highest sense of effectiveness. One-third of respondents had a moderate degree of depression. Of the respondents, 39% had a relatively high level of basic hope. The assessment of self-efficacy demonstrated that 52% of the respondents showed a high sense of self-efficacy, an average sense of self-efficacy was shown by 35.5% of the respondents, and a low sense of self-efficacy was shown by 12.6% of the respondents. Numerous hospitalized women during the COVID-19 pandemic, despite experiencing moderate depression, had an average sense of loneliness and a high level of hope and self-efficacy.

Interventional radiology plays a major role in oncology both for curative and palliative treatment, but few reports address post-procedural pain. The purpose of this study was to quantify postoperative pain after interventional radiology procedures in oncology and to identify major pain-associated pre and intraoperative factors.

With modern intensive care medicine, even older patients and those with pre-existing conditions can survive critical illnesses and major operations; however, unreflected application of intensive care treatment might lead to a state called chronic critical illness. Today, withholding treatment and/or treatment withdrawal precede many deaths in the intensice care unit (ICU). We looked at changes in measures at the end of life and withholding or withdrawal of treatment in the ICU of a German tertiary hospital in 2017/2018 compared to 2011/2012.

The placement of posterior mesh during pelvic organ prolapse laparoscopic surgery has been incriminated as responsible for postoperative adverse outcomes such as digestive symptoms, chronic pelvic pain, and sexual dysfunction. These complications may be related to neural injuries that occur during the fixation of the posterior mesh on the levator ani muscle.