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Low dose ketamine is a leading medication used to provide analgesia in pre-hospital and hospital settings. Low dose ketamine is increasingly used off-label to treat conditions such as depression. In animals, ketamine stimulates the sympathetic nervous system and increases blood pressure, but these physiological consequences have not been studied in conscious humans. Our data suggest that low dose ketamine administration blunts pain perception and reduces blood pressure, but not muscle sympathetic nerve activity burst frequency, responses during a cold pressor test in healthy humans. These mechanistic, physiological results inform risk-benefit analysis for clinicians administering low dose ketamine in humans.
Learn More >Monoclonal antibodies to calcitonin gene-related peptide or its receptor have clinical trial evidence in adults with headache, but data are lacking in adolescents. The objective of this study was to describe the safety and efficacy of calcitonin gene-related peptide monoclonal antibody treatment in adolescents with chronic headache disorders.
Learn More >Diagnostic uncertainty, the perceived lack of an accurate explanation of the patient's health problem, remains relatively unstudied in children. This study examined the prevalence, familial concordance, and correlates of diagnostic uncertainty in children and their parents presenting to a multidisciplinary pain clinic in the United States. One hundred and twenty-six parents and 91 of their children ( = 13.93 years, range = 8-18 years) completed a brief three-item measure of diagnostic uncertainty, as well as measures of pain-related distress and functioning. Forty-eight percent of children and 37% of parents believed something else was going on with the child's pain that doctors had not found out about yet. Across the three items, 66%-77% of children and their parents agreed in their endorsement of diagnostic uncertainty. Parents who believed that something else was going on with their child's pain had children with higher avoidance of pain-related activities ( = 5.601, = 0.020) and lower pain willingness ( = 4.782, = 0.032). Neither parent nor child diagnostic uncertainty was significantly related to the child's pain-related functioning. Diagnostic uncertainty, particularly in parents, is relevant in the experience of pediatric chronic pain and warrants further investigation as both a risk factor and therapeutic target.
Learn More >The development of persistent pain following total knee arthroplasty (TKA) is common, but its underlying mechanisms are unknown. The goal of the study was to assess brain grey matter structure and its correlation with function of the nociceptive system in people with good and poor outcomes following TKA.
Learn More >Musculoskeletal pain alters physiological function, which may be evidenced as early as middle age. Previous research has concluded that middle-aged adults are a high-risk group for musculoskeletal pain and report functional limitations similar to older adults. However, few studies have examined the relationships between musculoskeletal pain and physical function, using objective performance measures in a sample of racially and socioeconomically diverse adults. Thus, this study examined musculoskeletal pain in relation to physical function in middle-aged (30-64 years) White and Black adults, and investigated whether the relationship varied by sociodemographic characteristics.
Learn More >Neuropathic pain is a major problem following spinal cord injury (SCI). Central mechanisms involved in the modulation of nociceptive signals have been shown to be altered at the chronic stage, and it has been hypothesized that they might play a role in the development of chronic pain.
Learn More >Both parental and child factors have been previously associated with persistent or recurrent postoperative pain in children. Yet, little is known about the relative contribution of parent factors or whether child symptom factors might impact the association between parent factors and long-term pain. The aim of this study was to explore the associations between parent factors, child symptomology and the child's long-term pain outcomes after surgery.
Learn More >To evaluate whether quarterly or monthly administration of fremanezumab for migraine prevention exhibits a pattern of decreased efficacy towards the end of the dosing interval (wearing-off effect).
Learn More >Voltage-gated sodium (Na) channel subtypes, including Na1.7, are promising targets for the treatment of neurological diseases, such as chronic pain. Cone snail-derived µ-conotoxins are small, potent Na channel inhibitors which represent potential drug leads. Of the 22 µ-conotoxins characterised so far, only a small number, including KIIIA and CnIIIC, have shown inhibition against human Na1.7. We have recently identified a novel µ-conotoxin, SxIIIC, from . Here we present the isolation of native peptide, chemical synthesis, characterisation of human Na channel activity by whole-cell patch-clamp electrophysiology and analysis of the NMR solution structure. SxIIIC displays a unique Na channel selectivity profile (1.4 > 1.3 > 1.1 ≈ 1.6 ≈ 1.7 > 1.2 > 1.5 ≈ 1.8) when compared to other µ-conotoxins and represents one of the most potent human Na1.7 putative pore blockers (IC 152.2 ± 21.8 nM) to date. NMR analysis reveals the structure of SxIIIC includes the characteristic α-helix seen in other µ-conotoxins. Future investigations into structure-activity relationships of SxIIIC are expected to provide insights into residues important for Na channel pore blocker selectivity and subsequently important for chronic pain drug development.
Learn More >Chronic complications of traumatic brain injury (TBI) represent one of the greatest financial burdens and sources of suffering in society today. A substantial number of these patients suffer from post-traumatic headache (PTH), which is typically associated with tactile allodynia. Unfortunately, this phenomenon has been under-studied, in large part due to the lack of well-characterized laboratory animal models. We have addressed this gap in the field by characterizing the tactile sensory profile of two non-penetrating models of PTH. We show that multimodal TBI, administered by a jet-flow overpressure chamber that delivers a severe compressive impulse accompanied by a variable shock front and acceleration-deceleration insult, produces long term tactile hypersensitivity and widespread sensitization. These are phenotypes reminiscent of PTH in patients, in both cephalic and extracephalic regions. By contrast, closed head injury induces only transient cephalic tactile hypersensitivity, with no extracephalic consequences. Both models show a more severe phenotype with repetitive daily injury for three days, compared to either one or three successive injuries in a single day, providing new insight into patterns of injury that may place patients at greater risk of developing PTH. After recovery from transient cephalic tactile hypersensitivity, mice subjected to closed head injury demonstrate persistent hypersensitivity to established migraine triggers, including calcitonin gene-related peptide (CGRP) and sodium nitroprusside, a nitric oxide donor. Our results offer the field new tools for studying PTH, as well as preclinical support for a pathophysiologic role of CGRP in this condition.
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