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Anhedonia in endometriosis: An unexplored symptom.

Anhedonia is the diminished motivation and sensitivity to pleasurable stimuli. It has been reported to be more prevalent in patients with chronic pain as compared to healthy controls. Endometriosis is a chronic inflammatory systemic disease with a significant psychosocial impact that compromises wellbeing and the day-to-day life of patients. Women with endometriosis show significant psychological distress, even more pervasive when chronic pelvic pain is present. In the current review we will discuss the role of anhedonia in endometriotic chronic pelvic pain. We will also present new lines of research that could lead to more fully clarifying the psychological impact of endometriosis and its detrimental repercussions to quality of life and mental health.

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Cross-species comparisons reveal resistance of human skeletal stem cells to inhibition by non-steroidal anti-inflammatory drugs.

Fracture healing is highly dependent on an early inflammatory response in which prostaglandin production by cyclo-oxygenases (COX) plays a crucial role. Current patient analgesia regimens favor opioids over Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) since the latter have been implicated in delayed fracture healing. While animal studies broadly support a deleterious role of NSAID treatment to bone-regenerative processes, data for human fracture healing remains contradictory. In this study, we prospectively isolated mouse and human skeletal stem cells (SSCs) from fractures and compared the effect of various NSAIDs on their function. We found that osteochondrogenic differentiation of COX2-expressing mouse SSCs was impaired by NSAID treatment. In contrast, human SSCs (hSSC) downregulated COX2 expression during differentiation and showed impaired osteogenic capacity if COX2 was lentivirally overexpressed. Accordingly, short- and long-term treatment of hSSCs with non-selective and selective COX2 inhibitors did not affect colony forming ability, chondrogenic, and osteogenic differentiation potential . When hSSCs were transplanted ectopically into NSG mice treated with Indomethacin, graft mineralization was unaltered compared to vehicle injected mice. Thus, our results might contribute to understanding species-specific differences in NSAID sensitivity during fracture healing and support emerging clinical data which conflicts with other earlier observations that NSAID administration for post-operative analgesia for treatment of bone fractures are unsafe for patients.

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The effects of metformin in the treatment of osteoarthritis: Current perspectives.

Osteoarthritis is a chronic and irreversible disease of the locomotor system which is closely associated with advancing age. Pain and limited mobility frequently affect the quality of life in middle-aged and older adults. With a global population of more than 350 million, osteoarthritis is becoming a health threat alongside cancer and cardiovascular disease. It is challenging to find effective treatments to promote cartilage repair and slow down disease progression. Metformin is the first-line drug for patients with type 2 diabetes, and current perspectives suggest that it cannot only lower glucose but also has anti-inflammatory and anti-aging properties. Experimental studies applying metformin for the treatment of osteoarthritis have received much attention in recent years. In our review, we first presented the history of metformin and the current status of osteoarthritis, followed by a brief review of the mechanism that metformin acts, involving AMPK-dependent and non-dependent pathways. Moreover, we concluded that metformin may be beneficial in the treatment of osteoarthritis by inhibiting inflammation, modulating autophagy, antagonizing oxidative stress, and reducing pain levels. Finally, we analyzed the relevant evidence from animal and human studies. The potential of metformin for the treatment of osteoarthritis deserves to be further explored.

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RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation.

Patients with temporomandibular joint disorders (TMD) have high levels of inflammatory pain-related disability, which seriously affects their physical and mental health. However, an effective treatment is yet to be developed. Both circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) contribute to regulating pain conduction. In our current study, we report the expression profiles of circRNAs, lncRNAs, and mRNAs in the trigeminal ganglion (TG) associated with complete Freund's adjuvant (CFA)-induced TMD inflammation pain. The collected TGs from the experimental (CFA) and control (saline) groups were processed for deep RNA sequencing. Overall, 1078,909,068 clean reads were obtained. A total of 15,657 novel lncRNAs were identified, where 281 lncRNAs were differentially expressed on CFA3D and 350 lncRNAs were differentially expressed on CFA6D. In addition, a total of 55,441 mRNAs and 27,805 circRNAs were identified, where 3,914 mRNAs and 91 circRNAs were found differentially expressed, between the CFA3D and saline groups, while 4,232 mRNAs and 98 DE circRNAs were differentially expressed between the CFA6D and saline groups. Based on functional analyses, we found that the most significant enriched biological processes of the upregulated mRNAs were involved in the immunity, neuron projection, inflammatory response, MAPK signaling pathway, Ras signaling pathway, chemokine signaling pathway, and inflammatory response in TG. Further analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway suggest the involvement of dysregulated genes in the pain occurrence mechanism. Our findings provide a resource for expression patterns of gene transcripts in regions related to pain. These results suggest that apoptosis and neuroinflammation are important pathogenic mechanisms underlying TMD pain. Some of the reported differentially expressed genes might be considered promising therapeutic targets. The current research study revealed the expression profiles of circRNAs, lncRNAs, and mRNAs during TMD inflammation pain and sheds light on the roles of circRNAs and lncRNAs underlying the pain pathway in the trigeminal system of TMD inflammation pain.

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Pain acceptance and illness intrusiveness in low-back pain: A longitudinal study.

In chronic pain syndromes, acceptance of pain may be a better approach than pain control. So far, little data have been available on how pain and its acceptance affect illness intrusiveness among patients with low-back pain (LBP).

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Comparative efficacy of radiofrequency denervation in chronic low back pain: A systematic review and network meta-analysis.

Facet joint pain is a common cause of chronic low back pain (CLBP). Radiofrequency (RF) denervation is an effective treatment option.

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Source localized infraslow neurofeedback training in people with chronic painful knee osteoarthritis: A randomized, double-blind, sham-controlled feasibility clinical trial.

Persistent pain is a key symptom in people living with knee osteoarthritis (KOA). Infra-slow Neurofeedback (ISF-NF) training is a recent development focusing on modulating cortical slow-wave activity to improve pain outcomes. A parallel, two-armed double-blinded, randomized sham-controlled, feasibility clinical trial aimed to determine the feasibility and safety of a novel electroencephalography-based infraslow fluctuation neurofeedback (EEG ISF-NF) training in people with KOA and determine the variability of clinical outcomes and EEG changes following NF training. Eligible participants attended nine 30-min ISF-NF training sessions involving three cortical regions linked to pain. Feasibility measures were monitored during the trial period. Pain and functional outcomes were measured at baseline, post-intervention, and follow-up after 2 weeks. Resting-state EEG was recorded at baseline and immediate post-intervention. Participants were middle-aged (61.7 ± 7.6 years), New Zealand European (90.5%), and mostly females (62%) with an average knee pain duration of 4 ± 3.4 years. The study achieved a retention rate of 91%, with 20/22 participants completing all the sessions. Participants rated high levels of acceptance and "moderate to high levels of perceived effectiveness of the training." No serious adverse events were reported during the trial. Mean difference (95% CI) for clinical pain and function measures are as follows for pain severity [active: 0.89 ± 1.7 (-0.27 to 2.0); sham: 0.98 ± 1.1 (0.22-1.7)], pain interference [active: 0.75 ± 2.3 (-0.82 to 2.3); Sham: 0.89 ± 2.1 (-0.60 to 2.4)], pain unpleasantness [active: 2.6 ± 3.7 (0.17-5.1); sham: 2.8 ± 3 (0.62-5.0)] and physical function [active: 6.2 ± 13 (-2.6 to 15); sham: 1.6 ± 12 (-6.8 to 10)]. EEG sources demonstrated frequency-specific neuronal activity, functional connectivity, and ISF ratio changes following NF training. The findings of the study indicated that the ISF-NF training is a feasible, safe, and acceptable intervention for pain management in people with KOA, with high levels of perceived effectiveness. The study also reports the variability in clinical, brain activity, and connectivity changes following training.

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An LPAR -antagonist that reduces nociception and increases pruriception.

The G-protein coupled receptor LPAR plays a prominent role in LPA-mediated pain and itch signaling. In this study we focus on the LPAR-antagonist compound 3 (cpd3) and its ability to affect pain and itch signaling, both and .

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At Least 5-Year Outcomes of Whiplash-Induced Chronic Neck Pain Following Response to Intra-Articular Facet Joint Corticosteroid Injection.

To investigate whether the response to intra-articular facet joint corticosteroid injection can determine the long-term prognosis (at least 5 years after injury) of whiplash injury-related neck pain sustained 3-12 months after injury.

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Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human Cancer.

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is one of the most important natural products in the genus Due to its numerous biological effects, there has been extensive and increasing research interest in capsaicin, resulting in increased scientific publications in recent years. Therefore, an in-depth bibliometric analysis of published literature on capsaicin from 2001 to 2021 was performed to assess the global research status, thematic and emerging areas, and potential insights into future research. Furthermore, recent research advances of capsaicin and its combination therapy on human cancer as well as their potential mechanisms of action were described. In the last two decades, research outputs on capsaicin have increased by an estimated 18% per year and were dominated by research articles at 93% of the 3753 assessed literature. In addition, anti-cancer/pharmacokinetics, cytotoxicity, neurological and pain research studies were the keyword clusters generated and designated as thematic domains for capsaicin research. It was evident that the United States, China, and Japan accounted for about 42% of 3753 publications that met the inclusion criteria. Also, visibly dominant collaboration nodes and networks with most of the other identified countries were established. Assessment of the eligible literature revealed that the potential of capsaicin for mitigating cancer mainly entailed its chemo-preventive effects, which were often linked to its ability to exert multi-biological effects such as anti-mutagenic, antioxidant and anti-inflammatory activities. However, clinical studies were limited, which may be related to some of the inherent challenges associated with capsaicin in the limited clinical trials. This review presents a novel approach to visualizing information about capsaicin research and a comprehensive perspective on the therapeutic significance and applications of capsaicin in the treatment of human cancer.

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