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The Eutopic Endometrium Proteome in Endometriosis Reveals Candidate Markers and Molecular Mechanisms of Physiopathology.

Endometriosis is a common chronic gynaecological disease causing various symptoms, such as infertility and chronic pain. The gold standard for its diagnosis is still laparoscopy and the biopsy of endometriotic lesions. Here, we aimed to compare the eutopic endometrium from women with or without endometriosis to identify proteins that may be considered as potential biomarker candidates. Eutopic endometrium was collected from patients with endometriosis (n = 4) and women without endometriosis (n = 5) during a laparoscopy surgery during the mid-secretory phase of their menstrual cycle. Total proteins from tissues were extracted and digested before LC-MS-MS analysis. Among the 5301 proteins identified, 543 were differentially expressed and enriched in two specific KEGG pathways: focal adhesion and PI3K/AKT signaling. Integration of our data with a large-scale proteomics dataset allowed us to highlight 11 proteins that share the same trend of dysregulation in eutopic endometrium, regardless of the phase of the menstrual cycle. Our results constitute the first step towards the identification of potential promising endometrial diagnostic biomarkers. They provide new insights into the mechanisms underlying endometriosis and its etiology. Our results await further confirmation on a larger sample cohort.

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Rodent models of knee osteoarthritis for pain research.

Osteoarthritis (OA) is a chronic degenerative joint disease and a leading cause of disability worldwide. Pain is the main symptom, yet no current treatment can halt disease progression or effectively provide symptomatic relief. Numerous animal models have been described for studying OA and some for the associated OA pain. This review aims to update on current models used for studying OA pain, focusing on mice and rats. These models include surgical, chemical, mechanical, and spontaneous OA models. The impact of sex and age will also be addressed in the context of OA modelling. Although no single animal model has been shown ideal for studying OA pain, increased efforts to phenotype OA will likely impact the choice of models for pre-clinical and basic research studies.

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Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models.

Vocacapsaicin is a novel prodrug of trans-capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) being developed as a nonopioid, long-lasting, site-specific treatment for postsurgical pain management. The objective of these studies was to examine the safety and tolerability of vocacapsaicin in an osteotomy model in two animal species and to evaluate bone healing parameters. Rats undergoing unilateral femoral osteotomy received a single perioperative administration (by instillation) of vocacapsaicin (vehicle, 0.15, 0.3, and 0.6 mg/kg). Rabbits undergoing unilateral ulnar osteotomy received a single perioperative administration (by infiltration and instillation) of vocacapsaicin (vehicle, 0.256 and 0.52 mg) alone or in combination with 0.5% ropivacaine. Clinical signs, body weights, food consumption, radiography, histopathologic examinations, ex vivo bone mineral density measurements (rats only), and biomechanical testing were evaluated at 4 and 8 weeks in rats and at 2 and 10 weeks in rabbits. Plasma samples were also collected in rabbits. There were no vocacapsaicin-related effects on mortality, clinical observations, body weight, or food consumption in either species. Systemic exposure to vocacapsaicin and its metabolites, including capsaicin, was transient. In rats, vocacapsaicin was devoid of deleterious effects on bone healing parameters, and there was a trend for enhanced bone healing in rats treated with the mid-dose. In rabbits, vocacapsaicin administered alone or in combination with ropivacaine did not adversely affect bone healing parameters. In conclusion, a single perioperative administration of vocacapsaicin in unilateral osteotomy models was well tolerated, locally and systemically, supporting its continued development as a novel, nonopioid treatment for postsurgical pain management.

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Impact of Baseline Characteristics on the Efficacy and Safety of Eptinezumab in Patients With Migraine: Subgroup Analyses of PROMISE-1 and PROMISE-2.

In the PROMISE-1 (Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-1) and PROMISE-2 (Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-2) clinical trials, eptinezumab 100 mg and 300 mg met the primary efficacy end point, significantly reducing mean monthly migraine days across weeks 1 to 12. Clinical efficacy was also shown across key secondary end points. However, to determine if clinical efficacy varies across subgroups, it is necessary to determine efficacy in patients with different sociodemographic features and headache characteristics. These post hoc analyses of patients in PROMISE-1 and PROMISE-2 evaluated the impact of intrinsic factors on the efficacy and safety of eptinezumab in subgroups defined according to baseline demographic and migraine disease characteristics.

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Modulatory Effects of Stem Cells on Opioid Receptors and Neuroinflammation.

This narrative review examines stem cell therapy and its effect on opioid therapy in neuropathic pain.

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The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update.

Clinical practice guidelines.

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Duloxetine in OsteoArthritis (DOA) study: effects of duloxetine on pain and function in end-stage hip and knee OA – a pragmatic enriched randomized controlled trial.

Some osteoarthritis (OA) patients experience inadequate pain relief from analgesics like acetaminophen and nonsteroidal anti-inflammatory drugs. This could be the result of experienced non-nociceptive centralized pain. Placebo-controlled randomized trials (RCT) have proven the effectiveness of duloxetine for OA and several chronic pain conditions where central sensitization (CS) is one of the key underlying pain mechanisms.

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Dynamic brainstem and somatosensory cortical excitability during migraine cycles.

Migraine has complex pathophysiological characteristics and episodic attacks. To decipher the cyclic neurophysiological features of migraine attacks, in this study, we compared neuronal excitability in the brainstem and primary somatosensory (S1) region between migraine phases for 30 consecutive days in two patients with episodic migraine.

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Efficacy of photobiomodulation in reducing pain and improving the quality of life in patients with idiopathic burning mouth syndrome. A systematic review and meta-analysis.

Burning mouth syndrome is a chronic condition, which is characterised by a burning sensation or pain in the mucosa of the oral cavity. Treatment options include antidepressants, antipsychotics, anticonvulsants, analgesics, hormone replacement therapies and more recently photobiomodulation. This study aims to perform a systematic review with meta-analysis in order to determine the effect of photobiomodulation on pain relief and the oral health-related quality of life associated with this condition. A bibliographical search of the Pubmed, Embase, Web of Science and Scopus databases was conducted. Only randomised clinical trials were included. Pain and quality of life were calculated as mean difference and pooled at different treatment points (baseline = T0 and final time point = Tf) and laser modality. From a total of 103 records, 7 articles were retrieved for inclusion. PBM group had a greater decrease in pain than control group at Tf with a mean difference =  - 2.536 (IC 95% - 3.662 to - 1.410; I = 85.33%, p < 0.001). An improvement in oral health-related quality of life was observed in both groups, although this was more significant in the photobiomodulation group mean difference =  - 5.148 (IC 95% - 8.576 to - 1.719; I = 84.91%, p = 0.003). For the red laser, a greater improvement than infrared was observed, in pain, mean difference =  - 2.498 (IC 95% - 3.942 to - 1.053; I = 79.93%, p < 0.001), and in quality of life, mean difference =  - 8.144 (IC 95% - 12.082 to - 4.206; I = 64.22%, p = 0.027). Photobiomodulation, in particular, red laser protocols, resulted in improvement in pain and in quality of life of burning mouth syndrome patients.

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Are psychological interventions efficacious for adults with migraine? A systematic review and meta-analysis.

To determine the efficacy of psychological interventions in studies of adults with migraine, in reducing pain, and functional and psychosocial difficulties.

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