Rejected

Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein.

Non steroidal anti-inflammatory drugs (NSAIDs) are those of the most common over the counter (OTC) medications widely used by millions of people every day. Unfortunately, despite their popularity those drugs can cause serious side effect in the digestive system (ulcers, bleeding, and pain). These inconveniences are caused by the changes in the structures of the outer phospholipid layers of gastric mucus and mucosa. As a result the H ions from the stomach acid can pass easily through these natural protective barriers and damage the epithelial cells which causes ulcers and bleeding. Chitosan as a polysaccharide known for its unique biocompatibility, drug delivery possibilities and wound healing effect has been chosen to examine if it can induce the reduction of undesirable effects of naproxen. This paper focuses on the interactions of the naproxen with a model biological membrane with and without the presence of chitosan. Applying the Langmuir technique coupled with the surface potential measurements and the Brewster angle microscope imaging allowed to characterize successfully examined systems in terms of the monolayer fluidity changes, compressibility, thickness, stability, electric properties and morphology. The results proved that the presence of naproxen alters the mechanical and electrical properties of the model membrane depending on its surface pressure. Moreover, the addition of chitosan to the lipid-drug system causes significant changes in the properties of the layer, i.e. a reduction of its compressibility, thickness and morphology modification. Nevertheless, chitosan suppressed some changes induced by naproxen such as alteration of the dipole moment and film stability.

Stress plays a major role in the symptom burden of oncology patients and can exacerbate cancer chemotherapy-induced peripheral neuropathy (CIPN), a major adverse effect of many classes of chemotherapy. We explored the role of stress in the persistent phase of the pain induced by oxaliplatin. Oxaliplatin induced hyperalgesic priming, a model of the transition to chronic pain, as indicated by prolongation of hyperalgesia produced by prostaglandin E2 (PGE2), in male rats that was markedly attenuated in adrenalectomized rats. A neonatal handling protocol that induces stress-resilience in adult rats prevented oxaliplatin-induced hyperalgesic priming. To elucidate the role of the hypothalamic-pituitary adrenal and sympathoadrenal neuroendocrine stress axes in oxaliplatin CIPN, we used intrathecally administered antisense oligodeoxynucleotides (ODN) directed against mRNA for receptors mediating the effects of catecholamines and glucocorticoids, and their second messengers, to reduce their expression in nociceptors. While oxaliplatin-induced hyperalgesic priming was attenuated by intrathecal administration of β2-adrenergic and glucocorticoid receptor antisense ODNs, oxaliplatin-induced hyperalgesia was only attenuated by β2-adrenergic receptor antisense. Administration of pertussis toxin, a non-selective inhibitor of Gαi/o proteins, attenuated hyperalgesic priming. Antisense ODNs for Gαi1 and Gαo also attenuated hyperalgesic priming. Furthermore, antisense for protein kinase C epsilon, a second messenger involved in Type I hyperalgesic priming, also attenuated oxaliplatin-induced hyperalgesic priming. Inhibitors of second messengers involved in the maintenance of Type I (cordycepin) and Type II (SSU6656 and U0126) hyperalgesic priming both attenuated hyperalgesic priming. These experiments support a role for neuroendocrine stress axes in hyperalgesic priming, in male rats with oxaliplatin CIPN.

Cisplatin is a chemotherapeutic agent that is widely used to treat various types of cancers. However, its side effects, most commonly nausea and vomiting, limit its widespread use. Although various drugs, such as ondansetron and aprepitant, are used to alleviate these side effects, their efficacy is still debated. This review aims to summarize the results of 14 studies on the effects of seven single herbal extracts, one multiple herbal extract, and one ginger sub-component (i.e., [6]-gingerol) on cisplatin-induced nausea and vomiting. The results of the included studies were subdivided into four categories: kaolin consumption, retching and vomiting, food intake, and weight loss. Most studies used rodents, whereas four studies used minks or pigeons. The doses of cisplatin used in the studies varied from 3 mg/kg to 7.5 mg/kg, and only a single injection was used. Nine studies analyzed the mechanisms of action of herbal medicines and assessed the involvement of neurotransmitters, cytokines, enzymes, and various hematological parameters. Although further research is needed, this review suggests herbal medicine as a viable treatment option for cisplatin-induced neuropathic pain.

Chronic itch is the most prominent feature of atopic dermatitis (AD), and antihistamine treatment is often less effective in clinical pruritus severity in AD. Multiple studies have shown that histamine-independent itch pathways is thought to predominate in AD-induced chronic itch. Mas-related G-protein-coupled receptor (Mrgpr) A3 sensory neurons have been identified as one of the major itch-sensing neuron populations, and transient receptor potential (TRP) channel A1 is the key downstream of MrgprA3 mediated histamine-independent itch. MrgprA3-TRPA1 signal pathway is necessary for the development of chronic itch and may be the potentially promising target of chronic itch in AD. Dictamnine is one of the main quinoline alkaloid components of Cortex Dictamni (a traditional Chinese medicine widely used in clinical treatment of skin diseases). However, the anti-inflammatory and anti-pruritic effect of dictamnine on AD have not been reported. In this study, we used the 2,4-dinitrofluorobenzene (DNFB)-induced AD mouse model to observe the scratching behavior, inflammatory manifestations, and to detect the expression of MrgprA3 and TRPA1 in skin and DRG. The data demonstrated that dictamnine effectively inhibited AD-induced chronic itch, inflammation symptoms, epidermal thickening, inflammatory cell infiltration, and downregulates the expression of MrgprA3 and TRPA1. Furthermore, dictamnine restrained the excitability of MrgprA3 and TRPA1 neurons. Molecular docking also indicated that dictamnine has better binding affinity with MrgprA3. These results suggest that dictamnine may inhibit chronic itch caused by AD through the MrgprA3-TRPA1 mediated histamine-independent itch pathway, and may have a potential utility in AD treatment.

Central sensitization (CS) is defined as an increased nociceptive responsiveness due to sensitization of neurons in the central nervous system, usually the result of prolonged nociceptive input or a disease state associated with noxious inputs (e.g., polyarthritis). The concept of CS has recently been adopted in clinical assessments of chronic pain, but its diagnosis in humans may now includes a wide range of hypervigilant responses. The purpose of this review is to ascertain whether self-report questionnaires linked with CS are associated with enhanced nociceptive responses, or whether they measure sensitivity in a broader sense (i.e., emotional responses).According to our published, PROSPERO-registered review protocol (CRD42021208731), a predefined search of studies that involve the Central Sensitization Inventory (CSI) and/or Pain Sensitivity Questionnaire (PSQ) correlated with either nociceptive sensory tests or emotional hypervigilance was conducted on MEDLINE, PsychINFO and Web of Science. Correlations between the CSI/PSQ with our primary outcomes were extracted and meta-analysed.A Review of 66 studies totalling 13,284 participants found that the CSI (but not the PSQ) strongly correlated with psychological constructs: Depression, anxiety, stress, pain catastrophising, sleep and kinesiophobia. The CSI and PSQ showed weak/no correlations with experimental measures of nociceptive sensitivity: pain thresholds, temporal summation or conditioned pain modulation. The PSQ did however correlate strongly with phasic heat and tonic cold pain tests.The studies reviewed did not provide sufficient evidence that self-report measures reflect a canonical understanding of CS. The CSI more closely reflects psychological hypervigilance than increased responsiveness of nociceptive neurons.

Delayed cerebral ischemia (DCI) and vasospasm are two complications of subarachnoid hemorrhages (SAHs) which entail high risks of morbidity and mortality. However, it is unknown why only some patients who suffer SAHs will experience DCI and vasospasm. The purpose of this review is to describe the main genetic single nucleotide polymorphisms (SNPs) that have demonstrated a relationship with these complications. The SNP of the nitric oxide endothelial synthase (eNOS) has been related to the size and rupture of an aneurysm, as well as to DCI, vasospasm, and poor neurological outcome. The SNPs responsible for the asymmetric dimetilarginine and the high-mobility group box 1 have also been associated with DCI. An association between vasospasm and the SNPs of the eNOS, the haptoglobin, and the endothelin-1 receptor has been found. The SNPs of the angiotensin-converting enzyme have been related to DCI and poor neurological outcome. Studies on the SNPs of the Ryanodine Receptor yielded varying results regarding their association with vasospasm.

To compare characteristics of temporomandibular disorders (TMDs) in patients with rheumatoid arthritis (RA) to controls without RA.

Chronic migraine (CM) patients who report a high frequency and intensity of headaches also report neck pain (NP) and neck disability (ND) in neck activities that require stability. In this context, CM patients may report different headache intensities at different levels of ND. Our aim in this study is to investigate whether the intensity of headaches differs according to the level of ND in CM patients. Headache intensity and NP intensity were evaluated with the Visual Analog Scale (VAS), and ND was evaluated with the Neck Disability Index (NDI). A total of 142 patients who met the inclusion criteria were included in the study. The mean age was 53.24 ± 12.08 years. The median number of monthly headache days was 20. According to VAS, the median headache intensity was 10(4-10) cm and the median of NP intensity was 9(1-10) cm. The mean NDI was 28.45 ± 10.28. There was a difference in headache intensity between mild and severe disability levels ( = 0.007, Z = -3.289); headache intensity between mild and complete disability levels ( = 0.000, Z = -4.421); and headache intensity between moderate and complete disability levels ( = 0.004, Z = -2.212). Although the difference in headache intensity between ND levels is small, a median increase of 2 cm in headache intensity at mild ND levels may result in complete ND. A median increase of 1 cm in headache intensity at the moderate ND level may cause complete disability in the neck. According to our results, the intensity of headaches of CM patients differed according to the level of ND. We consider our results to be clinically important in this context.

Multiple vaccines have been tested in clinical trials for their efficacy and safety. In Saudi Arabia, Pfizer-BioNTech or Moderna were approved for children, however, previous studies to report their safety profile are limited. This research aims to understand the side effect of children's vaccination against SARS-CoV-2 infection in Saudi Arabia.