Articles: function.
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Functional reorganisation of the salience network (SN) has been proposed as one of the key pathomechanisms associated with central nociceptive processing in the chronic pain state. Being associated with an altered functional connectivity within the SN, these processes have been hypothesized to result from a loss of inhibitory function leading to node hyperexcitability and spontaneous pain. Combined resting-state BOLD functional magnetic resonance imaging (MRI) and 1 H-MR spectroscopy was applied to chronic back pain patients and healthy subjects to assess deviations from functional integrity (weighted closeness centrality [wCC], derived from resting-state functional MRI), oscillatory BOLD characteristics (spectral power), and neurotransmitter levels (GABA + , glutamate+glutamine) in 2 key SN nodes, anterior insular (aIns R ) and anterior mid-cingulate cortices. ⋯ The aIns R and, to a lesser extent, the anterior mid-cingulate of patients exhibited significantly reduced wCC accompanied by a spectral power shift from a lower to a higher frequency band, indicating a desynchronization of their neuronal activity within the SN, possibly because of increased spontaneous activations. Without revealing neurotransmitter differences, patients alone showed significant positive associations between local GABA + levels and wCC in aIns R , suggesting a stronger dependence of node synchronization on the inhibitory tone in the chronic pain state. However, this needs to be explored in the future using magnetic resonance spectroscopy techniques that are more sensitive to detecting subtle neurotransmitter changes and also allow multifocal characterization of neurotransmitter tone.
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Insomnia, which is characterized by persistent sleep difficulties in association with daytime dysfunction, is a common concern in clinical practice. Chronic insomnia disorder is defined as symptoms that occur at least 3 times per week and persist for at least 3 months. The American Academy of Sleep Medicine (AASM) published recent guidelines on behavioral and psychological treatment as well as pharmacologic therapy for chronic insomnia disorder. ⋯ Regarding pharmacologic treatment, the AASM, based on weak evidence, suggested a limited number of medications that might be useful and others that probably are not. Here, 2 clinicians with expertise in sleep disorders-one a clinical psychologist and the other a physician-debate the management of a patient with chronic insomnia who has been treated with medications. They discuss the role of behavioral and psychological interventions and pharmacologic therapy for chronic insomnia and how the primary care practitioner should approach such a patient.
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Central neuropathic pain is a core clinical sign of syringomyelia in humans and Cavalier King Charles Spaniel (CKCS) dogs. This histopathological study used spinal cords from CKCS dogs with syringomyelia to investigate the following conditions: (1) whether specific structural cervical spinal cord entities involved in nociception were affected by loss of neuroparenchyma or other pathological changes in CKCS dogs with pain-related behaviour and phantom scratching, (2) whether pain-related behaviour or phantom scratching correlated with loss of a specific anatomical entity or upregulation of glia cells, and (3) whether syringomyelia-related lesions affected specific functional spinal cord units of nociception. Spinal cord segments C1-C8 from CKCS dogs with magnetic resonance imaging-confirmed syringomyelia and clinical signs of pain and phantom scratching (n = 8) were compared with those from CKCS dogs without syringomyelia (n = 4). ⋯ A clear pattern of ipsilateral changes in the dorsal root entry zone characterised by deafferentation and reorganization of first-order axons into deeper laminae was found in cases with lateralised scratching. Significant changes in cell number density were not found for astrocytes or microglia, suggesting that the dogs represented cases of end-stage syringomyelia and thus could not reveal astrogliosis and microgliosis, which may be involved in the early phases of syrinx development and phantom scratching. The present relationship between clinical findings and dorsal horn and pain pathway pathology in CKCS dogs suggests that these dogs may be of interest as a supplement to experimental model pain research.
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Long-lasting local anesthetic use for perioperative pain control is limited by possible cardiotoxicity (e.g., arrhythmias and contractile depression), potentially leading to cardiac arrest. Off-target cardiac sodium channel blockade is considered the canonical mechanism behind cardiotoxicity; however, it does not fully explain the observed toxicity variability between anesthetics. The authors hypothesize that more cardiotoxic anesthetics (e.g., bupivacaine) differentially perturb other important cardiomyocyte functions (e.g., calcium dynamics), which may be exploited to mitigate drug toxicity. ⋯ Our data illustrate differences in calcium dynamics between anesthetics and how calcium may mitigate bupivacaine cardiotoxicity. Moreover, our findings suggest that bupivacaine cardiotoxicity risk may be higher than for ropivacaine in a calcium deficiency context.
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Eur. J. Intern. Med. · Dec 2022
Functional and metabolic frailty predicts mortality in patients undergoing TAVI: Insights from the OBSERVANT II study.
Despite the prognostic role of frailty among elderly patients undergoing transcatheter aortic valve implantation (TAVI) is known, its assessment still represents a challenge due to the multitude of scales proposed in literature. The aim of this study was to define the prognostic impact of a simple combined frailty model including both functional and metabolic parameters in a large cohort of patients undergoing TAVI with new generation devices. ⋯ In a large real-world cohort of patients undergoing TAVI with new generation devices, combined functional and metabolic frailty had a significant and incremental impact on 1-year mortality.