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Study protocol of the TEC-ORL clinical trial: a randomized comparative phase II trial investigating the analgesic activity of capsaicin vs Laroxyl in head and neck Cancer survivors presenting with neuropathic pain sequelae.

Neuropathic pain is common in cancer survivorship and is one of the most distressing symptoms for patients previously treated for head and neck cancer. Persistent neuropathic pain, when it is ongoing and uncontrolled, has a detrimental effect and erodes patients' quality of life. Patients treated for head and neck cancer are chronic opioid users to manage their post-treatment pain, which may entail an increased risk of addiction and overdose. We propose to evaluate the analgesic activity of high-concentration capsaicin patches for the treatment of head and neck cancer survivors presenting with neuropathic pain sequelae.

PACAP signaling is not involved in GTN- and levcromakalim-induced hypersensitivity in mouse models of migraine.

Calcitonin gene-related peptide (CGRP) antagonizing drugs represents the most important advance in migraine therapy for decades. However, these new drugs are only effective in 50-60% of patients. Recent studies have shown that the pituitary adenylate cyclase-activating peptide (PACAP38) pathway is independent from the CGRP signaling pathway. Here, we investigate PACAP38 signaling pathways in relation to glyceryl trinitrate (GTN), levcromakalim and sumatriptan.

A Guideline-Implementation Intervention to Improve the Management of Low Back Pain in Primary Care: A Difference-in-Difference-in-Differences Analysis.

Real-world adherence to clinical practice guidelines is often poor, resulting in sub-standard patient care and unnecessary healthcare costs. This study evaluates the effect of a guideline-implementation intervention for the management of low back pain (LBP) in general practice-the Fear Reduction Exercised Early (FREE) approach-on LBP-related injury insurance claims, healthcare utilisation, and costs of treatment.

Population perceived eye strain due to digital devices usage during COVID-19 pandemic.

To assess the magnitude severity and determinants of eyestrain and the use of digital devices in a Saudi population during the COVID-19 pandemic lockdown.

Long-term results of upfront, single-session Gamma Knife radiosurgery for large cystic vestibular schwannomas.

Anecdotally, cystic vestibular schwannomas (cVSs) are regarded to have unpredictable biologic activity with poorer clinical results, and most studies showed a less favorable prognosis following surgery. While stereotactic radiosurgery (SRS) is a well-established therapeutic option for small- to medium-sized VSs, cVSs are often larger, thus making upfront SRS more complicated. The purpose of this retrospective study was to assess the efficacy and safety of upfront SRS for large cVSs. The authors reviewed the data of 54 patients who received upfront, single-session Gamma Knife radiosurgery (GKRS) with a diagnosis of large cVS (> 4 cm3). Patients with neurofibromatosis type 2, multiple VSs, or recurrent VSs and < 24 months of clinical and neuroimaging follow-up were excluded. Hearing loss (48.1%) was the primary presenting symptom. The majority of cVSs were Koos grade IV (66.7%), and the most prevalent cyst pattern was "mixed pattern of small and big cysts" (46.3%). The median time between diagnosis and GKRS was 12 months (range, 1-147 months). At GKRS, the median cVS volume was 6.95 cm (range, 4.1-22 cm). The median marginal dose was 12 Gy (range, 10-12 Gy). The mean radiological and clinical follow-up periods were 62.2 ± 34.04 months (range, 24-169 months) and 94.9 ± 45.41 months (range, 24-175 months), respectively. At 2, 6, and 12 years, the tumor control rates were 100%, 95.7%, and 85.0%, respectively. Tumor shrinkage occurred in 92.6% of patients (n = 50), tumor volume remained stable in 5.6% of patients (n = 3), and tumor growth occurred in 1.9% of patients (n = 1). At a median follow-up of 53.5 months, the pre-GKRS tumor volume significantly decreased to 2.35 cm (p < 0.001). While Koos grade 3 patients had a greater possibility of attaining higher volume reduction, "multiple small thick-walled cyst pattern" and smaller tumor volumes decreased the likelihood of achieving higher volume reduction. Serviceable hearing (Gardner-Robertson Scale I-II) was present in 16.7% of patients prior to GKRS and it was preserved in all of these patients following GKRS. After GKRS, 1.9% of patients (n = 1) had new-onset trigeminal neuralgia. There was no new-onset facial palsy, hemifacial spasm, or hydrocephalus. Contrary to what was believed, our findings suggest that upfront GKRS seems to be a safe and effective treatment option for large cVSs.

Vasoconstriction and long-term headache in reversible cerebral vasoconstriction syndrome.

Angiographic vasoconstriction in reversible cerebral vasoconstriction syndrome (RCVS) is often undetectable at symptom onset and the diagnosis relies on clinical presentation. Although thunderclap headache is a hallmark feature of RCVS, the incidence and predictors of long-term headaches (LTH) are incompletely understood. Our study aims were twofold: to examine the sensitivity and specificity of a recently developed score (RCVS) for vasoconstriction detection in a real-world clinical context and describe the incidence and predictors of LTH beyond the acute phase of RCVS.

Emotion regulation and the salience network: a hypothetical integrative model of fibromyalgia.

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.

Sex differences in the inflammatory response of the mouse DRG and its connection to pain in experimental autoimmune encephalomyelitis.

Multiple Sclerosis (MS) is an autoimmune disease with notable sex differences. Women are not only more likely to develop MS but are also more likely than men to experience neuropathic pain in the disease. It has been postulated that neuropathic pain in MS can originate in the peripheral nervous system at the level of the dorsal root ganglia (DRG), which houses primary pain sensing neurons (nociceptors). These nociceptors become hyperexcitable in response to inflammation, leading to peripheral sensitization and eventually central sensitization, which maintains pain long-term. The mouse model experimental autoimmune encephalomyelitis (EAE) is a good model for human MS as it replicates classic MS symptoms including pain. Using EAE mice as well as naïve primary mouse DRG neurons cultured in vitro, we sought to characterize sex differences, specifically in peripheral sensory neurons. We found sex differences in the inflammatory profile of the EAE DRG, and in the TNFα downstream signaling pathways activated intracellularly in cultured nociceptors. We also found increased cell death with TNFα treatment. Given that TNFα signaling has been shown to initiate intrinsic apoptosis through mitochondrial disruption, this led us to investigate sex differences in the mitochondria's response to TNFα. Our results demonstrate that male sensory neurons are more sensitive to mitochondrial stress, making them prone to neuronal injury. In contrast, female sensory neurons appear to be more resistant to mitochondrial stress and exhibit an inflammatory and regenerative phenotype that may underlie greater nociceptor hyperexcitability and pain. Understanding these sex differences at the level of the primary sensory neuron is an important first step in our eventual goal of developing sex-specific treatments to halt pain development in the periphery before central sensitization is established.

Discrepancy between pain scores and need for analgesics.

Development and validation of a multivariable prediction model for the early prediction of chronic postsurgical pain. Response to Br J Anaesth 2022; 129: e155.

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