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Specialized pro-resolving mediators (SPMs) have demonstrated potent analgesic actions in animal models of pathological pain. The actions of SPMs in acute and chronic itch are currently unknown. Recently, n-3 docosapentaenoic acid (DPA) was found to be a substrate for the biosynthesis of several novel families of SPMs; 3-oxa-PD1n-3 DPA (3-oxa-PD1) is an oxidation-resistant metabolic stable analogue of the n-3 DPA-derived protectin D1 (PD1). Herein, we demonstrate that 3-oxa-PD1 effectively reduces both acute and chronic itch in mouse models. Intrathecal injection of 3-oxa-PD1 (100 ng) reduced acute itch induced by either histamine, chloroquine, or morphine. Furthermore, intrathecal 3-oxa-PD1 effectively reduced chronic itch, induced by cutaneous T cell lymphoma (CTCL), allergic contact dermatitis with dinitrofluorobenzene, and psoriasis by imiquimod. Intratumoral injection of 3-oxa-PD1 also suppressed CTCL-induced chronic itch. Strikingly, this anti-pruritic effect lasted for several weeks after 1-week of intrathecal 3-oxa-PD1 treatment. Whole-cell recordings revealed significant increase in excitatory postsynaptic currents in spinal dorsal horn (SDH) neurons of CTCL mice, but this increase was blocked by 3-oxa-PD1. 3-oxa-PD1 further increased inhibitory postsynaptic currents in SDH neurons of CTCL mice. CTCL increased the spinal levels of lipocalin-2 (LCN2), an itch mediator produced by astrocytes. 3-oxa-PD1 suppressed LCN2 production in CTCL mice and LCN2 secretion in astrocytes. Finally, CTCL-induced anxiety was alleviated by intrathecal 3-oxa-PD1. Our findings suggest that 3-oxa-PD1 potently inhibits acute and chronic itch via regulation of excitatory/inhibitory synaptic transmission and astroglial LCN2 production. Therefore, stable SPM analogs such as 3-oxa-PD1 could be useful to treat pruritus associated with different skin injuries.
Learn More >We examined long-term health outcomes associated with new persistent opioid use after surgery and hypothesized that patients with new persistent opioid use would have poorer overall health outcomes compared to those who did not develop new persistent opioid use after surgery.
Learn More >Approximately 60% of female migraineurs experience menstrual migraine (MM). Whether MM is a distinct clinical entity with more severe migraine attacks and a worse prognosis than nonmenstrual migraine (nMM) is still under debate. We conducted a systematic review and meta-analysis to investigate clinical differences between MM and nMM patients.
Learn More >Virtual reality (VR) is emerging as a new technology in the healthcare sector. It has been shown to enhance the patient's experience and satisfaction in various settings. This review aims to give a brief description of the use of VR and establish validity of its applications to improve the patient's pathway through surgery.
Learn More >Atopic dermatitis is a common chronic-relapsing, inflammatory and itchy eczematous skin disorder which occurs in both children and adults. AD pathogenesis is complex and several factors are implicated. Pruritus plays a pivotal role in disease's burden, significantly worsening atopic patient quality of life by limiting productivity and daily activities. AD diagnosis relies still on the experience of the healthcare professional and there are several unmet needs as for the diagnostic criteria, the management and the recognition of the burden of the disease. In this paper we present an indeep focus on the main clinical features of AD and the major unmet needs that should be addressed in the next research.
Learn More >The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) are used worldwide in adults. Until now, no adaptation for use in children has been proposed.
Learn More >Neurocytokines may upregulate or downregulate neuropathic pain. We hypothesized that dextrose (D-glucose) injections for therapeutic purposes (dextrose prolotherapy: DPT) in painful knee osteoarthritis (KOA) would favorably affect synovial-fluid neurocytokine concentrations.
Learn More >Migraine is a worldwide epidemic neurological disorder that has a significant influence on the quality of life. Migraine attacks are considered to be related to a calcitonin gene-related peptide (CGRP) signaling molecule, and anti-CGRP medications are used to abort and prevent migraine attacks. Erenumab, a monoclonal antibody that targets the CGRP receptor, is the first migraine preventive medication approved by the US Food and Drug Administration. In the present study, we evaluate the efficacy and safety of erenumab.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition impacting 30% of cancer survivors. This study is the first to explore whether a brain-based vulnerability to chronic sensory CIPN exists.
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