Rejected

High-intensity laser therapy (HILT) has been gaining popularity in the treatment of chronic musculoskeletal pain, including vulvodynia. The objective of this study was to critically appraise and synthesize the available evidence on the efficacy of HILT for reducing pain and improving function in vulvodynia and other chronic primary musculoskeletal pain conditions. Electronic databases and the grey literature were searched. Effects on pain intensity, function, and adverse events were assessed. One study investigating HILT in the treatment of vulvodynia and 13 studies on the treatment of chronic musculoskeletal pain were selected. The study assessing vulvodynia showed favorable results for reducing pain. Regarding chronic musculoskeletal pain, 12 out of the 13 studies selected consistently showed that HILT was more effective than the placebo/active comparator for reducing pain and improving function. The available effect sizes for pain showed large to huge effects. Similar effects were observed for function except for two studies showing moderate effects. The GRADE score was moderate. Conclusions: There are insufficient data to support the use of HILT in vulvodynia, but the promising results encourage further research. HILT appears to be effective in musculoskeletal pain conditions. More high-quality studies are needed to identify effective laser protocols.

This study explored the physical and psychological effects of scar massage on burn patients.

Autologous platelet-rich plasma (PRP) injection is an alternative treatment option for patients with lateral elbow tendinopathy. The treatment is supposed to accelerate tissue regeneration by providing high concentrations of growth factors derived from platelets. The aim of the study was to assess the relationship between the content of biologically active compounds in PRP and the clinical effect of the treatment. Thirty patients with lateral elbow tendinopathy treated with a single PRP injection, were evaluated. The pain intensity (measured by a visual analogue scale (VAS)), the pressure pain threshold (PPT), the grip strength and strength of the main arm and forearm muscle groups, and the functional outcome (measured by the Disability of Arm, Shoulder and Hand (DASH) and Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaires), were assessed before PRP injection and at one- and three-months follow-up. Flow cytometry measurements of the growth factors and inflammatory cytokines in PRP were performed, and the results were used to establish the relationship between those molecules and the clinical outcome. After three months from the intervention, the minimal clinically important difference in pain reduction and functional improvement was observed in 67% and 83% of patients, respectively. Positive correlations were found between the extent of pain reduction after three months and concentrations in the PRP of platelets, epidermal growth factor (EGF), vascular endothelial growth factor, and platelet-derived growth factors. The concentration of EGF in the PRP significantly correlated with an improvement in grip strength, strength of wrist extensors, and the size of functional improvement measured by the PRTEE. The local injection of PRP is a safe and effective treatment option for lateral elbow tendinopathy, and the clinical outcome is correlated with concentrations of its biologically active compounds.

Headache is one of the most prevalent, although often underreported, symptoms of coronavirus disease 2019 (COVID-19). It is generally accepted that this symptom is a form of secondary headache due to systemic viral infection. There are several hypotheses that try to explain its aetiopathogenesis. One of the most compelling is related to innate immune response to viral infection. This rationale is supported by similarities to other viral infections and the temporal overlap between immunological reactions and headache. Moreover, several key factors in innate immunity have been shown to facilitate headache e.g. interferons, interleukin (IL) -1-β, IL-6, and tumour necrosis factor. There is also a possibility that the virus causes headache by the direct activation of afferents through pattern recognition receptors (i.e. Toll-like receptor 7). Moreover, some data on post COVID-19 headache and after vaccination against SARS-CoV-2 infection suggests a similar cytokine-mediated pathomechanism in these clinical situations. Future research should look for evidence of causality between particular immune response factors and headache. Identifying key molecules responsible for headache during acute viral infection would be an important step towards managing one of the most prevalent secondary headache disorders.

Nociplastic pain has been introduced by the IASP as a third category of pain, distinct from nociceptive and neuropathic pain. Pathogenetically, it is considered to be a continuum of these two types of pain after becoming chronic. Repetitive peripheral painful stimulation causes a central sensitization with hypersensitivity of the corresponding spinal metamer or brain region. Therefore, signs of altered nociception, such as allodynia, may be found on the tissues of the related dermatome, myotome and sclerotome, and characterize nociplastic pain. This kind of pain was found in over 20% of people with multiple sclerosis (pwMS), a demyelinating autoimmune disease that affects the central nervous system. Nociplastic pain may be an amplifier of spasticity, the main pyramidal symptom that affects about 80% of pwMS. This article details the case of a 36-year-old woman with multiple sclerosis who was affected by spasticity and non-specific pain of the lower limbs, disabling on walking. Previous analgesic and muscle relaxant treatment had no benefits. The diagnosis of nociplastic pain on the cutaneous tissue of the anterolateral region of the left thigh and its treatment with intradermal normal saline injection on the painful skin area showed immediate and lasting effects on pain and spasticity, improving significantly the patient's balance and walking, as assessed by a 3D motion analysis and rating scales.

Refractory angina represents the final stage of chronic coronary artery disease, where anginal symptoms persist despite complete epicardial coronary artery revascularization and maximally tolerated pharmacological therapy. Percutaneous narrowing of the coronary sinus with the Coronary Sinus Reducer device was first attempted in humans in 2005 and has been shown to improve angina symptoms and the quality of life of patients suffering chronic refractory angina. It was recently included in the European guidelines for the management of chronic coronary syndrome and is progressively gaining popularity. The authors hereby provide a review of current literature on the topic, intending to facilitate insights and to promote further research on this device and its clinical applications.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide known to be involved in the trigeminovascular system and to function as a potent vasodilator. Although it has emerged as a viable target for headache management with targeted treatments developed for migraine, a highly disabling neurovascular disorder, less is known about CGRP's role in other neurologic conditions such as traumatic brain injury and subarachnoid hemorrhage. The literature has shown that during these injury cascades, CGRP receptors are modulated in varying ways. Therefore, CGRP or its receptors might be viable targets to manage secondary injuries following acute brain injury. In this review, we highlight the pathophysiology of the CGRP pathway and its relation to migraine pathogenesis. Using these same principles, we assess the existing preclinical data for CGRP and its role in acute brain injury. The findings are promising, and set the basis for further work, with specific focus on the therapeutic benefit of CGRP modulation following neurologic injury.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, which is characterized by massive pain and destruction of synovial joints, leads to bone erosion, damage to cartilage, and disability. Several studies suggested that resveratrol supplementation may be effective in the prevention and management of RA. Therefore, a systematic review was conducted to summarize published studies that assess the effect of resveratrol supplementation on the complications of RA.

Insertional Achilles tendinopathy is a common overuse disorder affecting the foot and ankle that can lead to the development of a Haglund's deformity with chronicity, a retrocalcaneal exostosis that forms at the Achilles insertion site, further increasing pain and dysfunction.

Nitric oxide (NO) is a key molecule in the biology of human life. NO is involved in the physiology of organ viability and in the pathophysiology of organ dysfunction, respectively. In this narrative review, we aimed at elucidating the mechanisms behind the role of NO in the respiratory and cardio-cerebrovascular systems, in the presence of a healthy or dysfunctional endothelium. NO is a key player in maintaining multiorgan viability with adequate organ blood perfusion. We report on its physiological endogenous production and effects in the circulation and within the lungs, as well as the pathophysiological implication of its disturbances related to NO depletion and excess. The review covers from preclinical information about endogenous NO produced by nitric oxide synthase (NOS) to the potential therapeutic role of exogenous NO (inhaled nitric oxide, iNO). Moreover, the importance of NO in several clinical conditions in critically ill patients such as hypoxemia, pulmonary hypertension, hemolysis, cerebrovascular events and ischemia-reperfusion syndrome is evaluated in preclinical and clinical settings. Accordingly, the mechanism behind the beneficial iNO treatment in hypoxemia and pulmonary hypertension is investigated. Furthermore, investigating the pathophysiology of brain injury, cardiopulmonary bypass, and red blood cell and artificial hemoglobin transfusion provides a focus on the potential role of NO as a protective molecule in multiorgan dysfunction. Finally, the preclinical toxicology of iNO and the antimicrobial role of NO-including its recent investigation on its role against the Sars-CoV2 infection during the COVID-19 pandemic-are described.