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Chronic pain and health inequalities: why we need to act.

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Pilot Investigation of Somatosensory Functioning and Pain Catastrophizing in Pediatric Spinal Fusion Surgery.

Chronic post-surgical pain (CPSP) is a significant concern and contributes to the opioid epidemic; however, little is known about CPSP in young people.

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RAR-alpha: Creator, protector, and tormentor.

Retinoic acid receptors are important for homeostatic synaptic plasticity and have many beneficial effects within the brain. New work by Cao et al. uncovers a role for these receptors in driving neuropathic pain development, thus identifying a potential preventative therapeutic target.

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Choosing the appropriate pharmacotherapy for nonspecific chronic low back pain.

The pharmacological management of nonspecific chronic low back pain (NCLBP) aims to restore daily activities and improve the quality of life. No magic bullet exists for NCLBP; interventions to reduce pain and disability are available, but long-term results are unpredictable. Education in this regard needs to improve. This is often hard to accept for clinicians and patients, and provides a fertile soil to quacks, faith healers, and gurus to promote miraculous non-evidence-based solutions. The management of NCLBP is not well codified and extremely heterogeneous, and residual symptoms are common. Depending on the individual severity of NCLPB, pharmacological management may range from nonopioid to opioid analgesics. It is important to identify patients with generalized sensory hypersensitivity, who may benefit from a dedicated therapy. In this editorial, we provide an evidenced-based overview of the principles of pharmacological management of NCLPB.

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Opening the amino acid toolbox for peptide-based NTS2-selective ligands as promising lead compounds for pain management.

Chronic pain is one of the most critical health issues worldwide. Despite considerable efforts to find therapeutic alternatives, opioid drugs remain the gold standard for pain management. The administration of μ-opioid receptor (MOR) agonists is associated with detrimental and limiting adverse effects. Overall, these adverse effects strongly overshadow the effectiveness of opioid therapy. In this context, the development of neurotensin (NT) ligands has shown to be a promising approach for the management of chronic and acute pain. NT exerts its opioid-independent analgesic effects through the binding of two G protein-coupled receptors (GPCRs), NTS1 and NTS2. In the last decades, modified NT analogues have been proven to provide potent analgesia in vivo. However, selective NTS1 and non-selective NTS1/NTS2 ligands cause antinociception associated with hypothermia and hypotension, whereas selective NTS2 ligands induce analgesia without altering the body temperature and blood pressure. In light of this, various structure-activity relationship (SAR) studies provided for findings addressing the binding affinity of ligands towards NTS2. Herein, we comprehensively review peptide-based NTS2-selective ligands as a robust alternative for future pain management. Particular emphasis is placed on SAR studies governing the desired selectivity and associated in vivo results.

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CircFOXK2 Promotes the Progression of Osteoarthritis by Regulating the miR-4640-5p/NOTCH2 Axis.

Osteoarthritis (OA) is the most common age-related chronic and disabling joint disease, frequently causing pain and disability in the adult population. Given that there are no proven disease-modifying drugs for OA, it is urgent to gain a deeper understanding of OA pathogenesis. This study intended to uncover the circFOXK2 regulation in OA.

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A positive feedback loop of heparanase/syndecan1/nerve growth factor regulates cancer pain progression.

The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)/nerve growth factor (NGF) on cancer pain from melanoma.

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Migraine Disability and Severity Improvement during Long-Term Treatment with Erenumab.

The aim of the present study was to assess erenumab efficacy in migraine disability and intensity throughout the first treatment cycle, discontinuation, and the first 6 months of re-treatment in patients with high-frequency episodic migraine. The study design was retrospective and observational. Inclusion criteria were the following: diagnosis of high-frequency episodic migraine and ongoing treatment with erenumab 140 mg currently at their second treatment cycle. Data regarding migraine frequency, disability (MIDAS score), and severity of attacks (NRS score) were collected quarterly. Twenty-five patients were enrolled. At the end of the first treatment cycle, compared to baseline, a significant improvement of MIDAS scores was found (13.5 ± 11.1 vs. 72.5 ± 32.1; p = 0.005), with a subsequent worsening during treatment suspension (30.1 ± 26.9; p = 0.03). Pain intensity remained unmodified during the first treatment cycle (NRS score baseline: 7.6 ± 0.9 vs. 12 months: 7.5 ± 0.7; p = 0.13). During re-treatment, MIDAS scores documented a new significant improvement, reaching the same level at 6 months of re-treatment as at the end of the first cycle (30.1 ± 26.9 vs. 12.9 ± 5.4; p = 0.03). A significant improvement, compared to baseline, was observed for pain intensity during re-treatment (6.8 ± 2.2 vs. 5.6 ± 0.9 at RT3 vs. 5.2 ± 1.4 at RT6; p = 0.05). In conclusion, during re-treatment with erenumab 140 mg, migraine pain intensity and disability documented a significant and progressive improvement. Our data confirm the long-term efficacy, although in a very limited case series, of monoclonal antibodies targeting CGRP beyond headache frequency reduction.

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Randomized Controlled Study to Evaluate the Efficacy and Safety of Soticlestat as Adjunctive Therapy in Adults with Complex Regional Pain Syndrome.

The objective was to investigate the efficacy and safety of soticlestat as adjunctive therapy in participants with complex regional pain syndrome (CRPS).

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Conservative Therapy for Acute and Subacute Back or Neck Pain.

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