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The primary objective was to compare the serum brain-derived neurotrophic factor (BDNF) level in the patients with two types of pain: fibromyalgia (FM) and non-FM nociceptive pain (non-FM NP). The secondary objective was to investigate the effect of duloxetine on serum BDNF in FM patients and assess the direction of BDNF changes' relation to clinical parameters' alterations.
Learn More >Despite the effort on developing new treatments, therapy for neuropathic pain is still a clinical challenge and combination therapy regimes of two or more drugs are often needed to improve efficacy. Accumulating evidence shows an altered expression and activity of histone acetylation enzymes in chronic pain conditions and restoration of these aberrant epigenetic modifications promotes pain-relieving activity. Recent studies showed a synergistic activity in neuropathic pain models by combination of histone deacetylases (HDACs) and bromodomain and extra-terminal domain (BET) inhibitors. On these premises, the present study investigated the pharmacological profile of new dual HDAC/BRD4 inhibitors, named SUM52 and SUM35, in the spared nerve injury (SNI) model in mice as innovative strategy to simultaneously inhibit HDACs and BETs. Intranasal administration of SUM52 and SUM35 attenuated thermal and mechanical hypersensitivity in the absence of locomotor side effects. Both dual inhibitors showed a preferential interaction with BRD4-BD2 domain, and SUM52 resulted the most active compound. SUM52 reduced microglia-mediated spinal neuroinflammation in spinal cord sections of SNI mice as showed by reduction of IBA1 immunostaining, inducible nitric oxide synthase (iNOS) expression, p65 nuclear factor-κB (NF-κB) and p38 MAPK over-phosphorylation. A robust decrease of the spinal proinflammatory cytokines content (IL-6, IL-1ß) was also observed after SUM52 treatment. Present results, showing the pain-relieving activity of HDAC/BRD4 dual inhibitors, indicate that the simultaneous modulation of BET and HDAC activity by a single molecule acting as multi-target agent might represent a promise for neuropathic pain relief.
Learn More >An excitatory neuron subset in the spinal dorsal horn (SDH) that expresses gastrin-releasing peptide receptors (GRPR) is critical for pruriceptive transmission. Here, we show that glutamatergic excitatory inputs onto GRPR neurons are facilitated in mouse models of chronic itch. In these models, neuronal pentraxin 2 (NPTX2), an activity-dependent immediate early gene product, is upregulated in the dorsal root ganglion (DRG) neurons. Electron microscopy reveals that NPTX2 is present at presynaptic terminals connected onto postsynaptic GRPR neurons. NPTX2-knockout prevents the facilitation of synaptic inputs to GRPR neurons, and repetitive scratching behavior. DRG-specific NPTX2 expression rescues the impaired behavioral phenotype in NPTX2-knockout mice. Moreover, ectopic expression of a dominant-negative form of NPTX2 in DRG neurons reduces chronic itch-like behavior in mice. Our findings indicate that the upregulation of NPTX2 expression in DRG neurons contributes to the facilitation of glutamatergic inputs onto GRPR neurons under chronic itch-like conditions, providing a potential therapeutic target.
Learn More >Persistent/chronic inflammatory pain involves multiple pathophysiological mechanisms and is far more complex than acute/momentary pain. Current therapeutics for chronic inflammatory pain are often not effective because the etiology responsible for the pain is not addressed by traditional pharmacological treatments. Cathepsin K is a cysteine protease that has mostly been studied in the context of bone and joint disorders. Previous work by others has shown that inhibition of cathepsin K activity reduces osteoarthritis-associated nociception in joints. However, the role of cathepsin K in cutaneous inflammation is understudied. We assessed the effectiveness of genetic deletion or pharmacological inhibition of cathepsin K in male mice on the expression of nocifensive behaviors after formalin injection or mechanical and thermal hypersensitivity after injection of complete Freund's adjuvant (CFA) into the mouse hind paw. Our data demonstrate that cathepsin K knockout mice (Ctsk) have a reduction in nocifensive behaviors in the formalin test. In addition, Ctsk do not develop mechanical hypersensitivity after CFA injection for up to 7 days. Moreover, we found that inhibition of cathepsin K reduced mechanical hypersensitivity after CFA injection and mRNA levels, protein levels, and cathepsin K activity levels were elevated after CFA injection. Based upon our data, cathepsin K is indicated to play a role in the expression of chemically-induced cutaneous hypersensitivity, as Ctsk mice do not develop mechanical hypersensitivity and show a reduction in nocifensive behaviors. Further research is needed to determine whether attenuating cathepsin K activity may generate a clinically relevant therapeutic.
Learn More >The aim of this study was to assess the impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the quality of life (QoL) of people with ME/CFS and their relative or partner (family member).
Learn More >Repression has been linked to greater illness, somatic symptoms, and poorer physical health, both in adult and pediatric populations. The current study examined psychological and pain profiles of children with chronic pain who may under-report levels of psychological distress at a first interdisciplinary chronic pain assessment. Children and their caregiver completed measures of psychopathology and pain intensity, while clinicians rated their levels of disability. Based on self-report measures, children were classified as "repressors" (low anxiety/high social desirability) or as "true low anxious" (low anxiety/low social desirability). Groups were then compared on psychological and pain characteristics. Compared to children with true low anxiety, repressors reported lower levels of depressive and somatic symptoms but provided higher ratings on pain intensity, pain-unpleasantness, and self-oriented perfectionism. Caregivers of repressors rated their children as having higher levels of adaptability compared to caregivers of children in the true low anxious group. Groups did not differ on clinician-rated level of disability. Children classified as repressors exhibited different profiles than children classified as having true low anxiety on both psychological outcomes and pain characteristics. Repression may be an important factor to consider for those assessing and treating children with chronic pain.
Learn More >To examine inequities in pain assessment and management of hospitalized children with limited English proficiency (LEP) as assessed by (1) self-reported pain prevalence and intensity, and (2) nurse-documented pain assessments and analgesia.
Learn More >Idiopathic intracranial hypertension syndrome (IIH) is a pathology characterized by headache, visual disturbances, papilledema, increased cerebrospinal fluid pressure with normal cytochemistry that is not attributable to cerebral structural alterations. This study aimed to describe the usefulness of cerebral angiography in the diagnostic approach and management of patients with clinical suspicion of IIH at a fourth level hospital in Cali, Colombia.
Learn More >The gut microbiome plays critical roles in human health and disease. Recent studies suggest it may also be associated with chronic pain and postoperative pain outcomes. In animal models, the composition of the gut microbiome changes after general anesthesia and affects the host response to medications, including anesthetics and opioids. In humans, the gut microbiome is associated with the development of postoperative pain and neurocognitive disorders. Additionally, the composition of the gut microbiome has been associated with pain conditions including visceral pain, nociplastic pain, complex regional pain syndrome, and headaches, partly through altered concentration of circulating bacterial-derived metabolites. Furthermore, animal studies demonstrate the critical role of the gut microbiome in neuropathic pain via immunomodulatory mechanisms. This article reviews basic concepts of the human gut microbiome and its interactions with the host and provide a comprehensive overview of the evidence linking the gut microbiome to anesthesiology, critical care, and pain medicine.
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