Accepted

Fibromyalgia is a rheumatic disease with no specific laboratory markers and is insensitive to hormonal drugs and nonsteroidal anti-inflammatory drugs commonly used to treat rheumatism. Guidelines recommend that non-pharmacological therapy should be the first-line treatment for fibromyalgia. Since the publication of the first diagnostic criteria for fibromyalgia in 1990, studies on acupuncture for fibromyalgia have been reported periodically. This study aims to explore the intellectual landscape of acupuncture for fibromyalgia since 1990, and to identify research trends and fronts in this field.

Artificial intelligence (AI) algorithms have been applied to diagnose temporomandibular disorders (TMDs). However, studies have used different patient selection criteria, disease subtypes, input data, and outcome measures. Resultantly, the performance of the AI models varies.

Endometriosis is defined as the presence of endometrial-like glands and stroma located outside the uterine cavity. This common, estrogen dependent, inflammatory condition affects up to 15% of reproductive-aged women and is a well-recognized cause of chronic pelvic pain and infertility. Despite the still unknown etiology of endometriosis, much evidence suggests the participation of epigenetic mechanisms in the disease etiopathogenesis. The main rationale is based on the fact that heritable phenotype changes that do not involve alterations in the DNA sequence are common triggers for hormonal, immunological, and inflammatory disorders, which play a key role in the formation of endometriotic foci. Epigenetic mechanisms regulating T-cell responses, including DNA methylation and posttranslational histone modifications, deserve attention because tissue-resident T lymphocytes work in concert with organ structural cells to generate appropriate immune responses and are functionally shaped by organ-specific environmental conditions. Thus, a failure to precisely regulate immune cell transcription may result in compromised immunological integrity of the organ with an increased risk of inflammatory disorders. The coexistence of endometriosis and autoimmunity is a well-known occurrence. Recent research results indicate regulatory T-cell (Treg) alterations in endometriosis, and an increased number of highly active Tregs and macrophages have been found in peritoneal fluid from women with endometriosis. Elimination of the regulatory function of T cells and an imbalance between T helper cells of the Th1 and Th2 types have been reported in the endometria of women with endometriosis-associated infertility. This review aims to present the state of the art in recognition epigenetic reprogramming of T cells as the key factor in the pathophysiology of endometriosis in the context of T-cell-related autoimmunity. The new potential therapeutic approaches based on epigenetic modulation and/or adoptive transfer of T cells will also be outlined.

General fatigue, sleep-related fatigue, and cognitive fatigue are prevalent and disruptive in adults with chronic musculoskeletal (MSK) pain, but little is known about these fatigue subtypes in pediatric musculoskeletal pain.

Understanding mechanisms that underly the transition from acute to chronic pain and identifying potential targets for preventing or minimizing this progression have specific relevance for chronic postsurgical pain (CPSP). Though it is clear that multiple psychosocial, family, and environmental factors may influence CPSP, this review will focus on parallels between clinical observations and translational laboratory studies investigating the acute and long-term effects of surgical injury on nociceptive pathways. This includes data related to alterations in sensitivity at different points along nociceptive pathways from the periphery to the brain; age- and sex-dependent mechanisms underlying the transition from acute to persistent pain; potential targets for preventive interventions; and the impact of prior surgical injury. Ongoing preclinical studies evaluating age- and sex-dependent mechanisms will also inform comparative efficacy and preclinical safety assessments of potential preventive pharmacological interventions aimed at reducing the risk of CPSP. In future clinical studies, more detailed and longitudinal peri-operative phenotyping with patient- and parent-reported chronic pain core outcomes, alongside more specialized evaluations of somatosensory function, modulation, and circuitry, may enhance understanding of individual variability in postsurgical pain trajectories and improve recognition and management of CPSP.

Ketamine is administered predominantly the intravenous route for the various indications, including anesthesia, pain relief and treatment of depression. Here we report on the pharmacokinetics of sublingual and buccal fast-dissolving oral-thin-films that contain 50 mg of -ketamine in a population of healthy male and female volunteers. Twenty volunteers received one or two oral thin films on separate occasions in a randomized crossover design. The oral thin films were placed sublingually ( = 15) or buccally ( = 5) and left to dissolve for 10 min in the mouth during which the subjects were not allowed to swallow. For 6 subsequent hours, pharmacokinetic blood samples were obtained after which 20 mg -ketamine was infused intravenously and blood sampling continued for another 2-hours. A population pharmacokinetic analysis was performed in NONMEM pharmacokinetic model of -ketamine and its metabolites -norketamine and -hydroxynorketamine; < 0.01 were considered significant. -ketamine bioavailability was 26 ± 1% (estimate ± standard error of the estimate) with a 20% lower bioavailability of the 100 mg oral thin film relative to the 50 mg film, although this difference did not reach the level of significance. Due to the large first pass-effect, 80% of -ketamine was metabolized into -norketamine leading to high plasma levels of -norketamine following the oral thin film application with 56% of -ketamine finally metabolized into -hydroxynorketamine. No differences in pharmacokinetics were observed for the sublingual and buccal administration routes. The -ketamine oral thin film is a safe and practical alternative to intravenous -ketamine administration that results in relatively high plasma levels of -ketamine and its two metabolites.

Osteoarthritis is a common age-related joint degenerative disease. Pain, swelling, brief morning stiffness, and functional limitations are its main characteristics. There are still no well-established strategies to cure osteoarthritis. Therefore, better clarification of mechanisms associated with the onset and progression of osteoarthritis is critical to provide a theoretical basis for the establishment of novel preventive and therapeutic strategies. Chondrocytes exist in a hypoxic environment, and HIF-1α plays a vital role in regulating hypoxic response. HIF-1α responds to cellular oxygenation decreases in tissue regulating survival and growth arrest of chondrocytes. The activation of HIF-1α could regulate autophagy and apoptosis of chondrocytes, decrease inflammatory cytokine synthesis, and regulate the chondrocyte extracellular matrix environment. Moreover, it could maintain the chondrogenic phenotype that regulates glycolysis and the mitochondrial function of osteoarthritis, resulting in a denser collagen matrix that delays cartilage degradation. Thus, HIF-1α is likely to be a crucial therapeutic target for osteoarthritis regulating chondrocyte inflammation and metabolism. In this review, we summarize the mechanism of hypoxia in the pathogenic mechanisms of osteoarthritis, and focus on a series of therapeutic treatments targeting HIF-1α for osteoarthritis. Further clarification of the regulatory mechanisms of HIF-1α in osteoarthritis may provide more useful clues to developing novel osteoarthritis treatment strategies.

The sensory experience of pain depends not only on the transmission of noxious information (nociception), but on the state of the body in a biological, psychological, and social milieu. A brainstem pain-modulating system with its output node in the rostral ventromedial medulla (RVM) can regulate the threshold and gain for nociceptive transmission. This review considers the current understanding of how RVM pain-modulating neurons, namely ON-cells and OFF-cells, are engaged by "top-down" cognitive and emotional factors, as well as by "bottom-up" sensory inputs, to enhance or suppress pain.