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Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and […]
Learn More >A growing body of evidence suggests that intractable pain reduces both the quality of life and survival in cancer patients. In the present study, we evaluated whether chronic pain stimuli […]
Learn More >Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and central nervous system. Additionally, it also mediates non-histaminergic itch and pathological itch conditions in mice. Thus, GRPR could be an attractive target for cancer and itch therapy. Here, we report the inactive state crystal structure of human GRPR in complex with the non-peptide antagonist PD176252, as well as two active state cryo-electron microscopy (cryo-EM) structures of GRPR bound to the endogenous peptide agonist gastrin-releasing peptide and the synthetic BBN analog [D-Phe, β-Ala, Phe, Nle] Bn (6-14), in complex with G heterotrimers. These structures revealed the molecular mechanisms for the ligand binding, receptor activation, and G proteins signaling of GRPR, which are expected to accelerate the structure-based design of GRPR antagonists and agonists for the treatments of cancer and pruritus.
Learn More >Chronic pain is a complex clinical condition, often devastating for patients and unmanageable with pharmacological treatments. Converging evidence suggests that transcutaneous spinal Direct Current Stimulation (tsDCS) might represent a complementary therapy in managing chronic pain. In this randomized, double-blind and sham-controlled crossover study, we assessed tsDCS effects in chronic pain patients. Sixteen patients (aged 65.06 ± 16.16 years, eight women) with chronic pain of different etiology underwent sham and anodal tsDCS (anode over the tenth thoracic vertebra, cathode over the somatosensory cortical area: 2.5 mA, 20 min, 5 days for 1 week). As outcomes, we considered the Visual Analog Scale (VAS), the Neuropathic Pain Symptom Inventory (NPSI), and the components of the lower limb flexion reflex (LLFR), i.e., RIII threshold, RII latency and area, RIII latency and area, and flexion reflex (FR) total area. Assessments were conducted before (T0), immediately at the end of the treatment (T1), after 1 week (T2) and 1 month (T3). Compared to sham, anodal tsDCS reduced RIII area at T2 ( = 0.0043) and T3 ( = 0.0012); similarly, FR total area was reduced at T3 ( = 0.03). Clinically, anodal tsDCS dampened VAS at T3 ( = 0.015), and NPSI scores at T1 ( = 0.0012), and T3 ( = 0.0015), whereas sham condition left them unchanged. Changes in VAS and NPSI scores linearly correlated with the reduction in LLFR areas ( = 0.0004). Our findings suggest that tsDCS could modulate nociceptive processing and pain perception in chronic pain syndromes.
Learn More >Neuropathic pain (NP) associated with depression or anxiety is highly prevalent in clinical practice. Publications about NP associated with depression or anxiety increased exponentially from 2000 to 2020. However, studies that applied the bibliometric method in analyzing global scientific research about NP associated with depression or anxiety are rare. This work used the bibliometric method to analyze the publications on NP associated with depression or anxiety between 2000 and 2020. Publications from 2000 and 2020 were identified from the Thomson Reuters Web of Science (WoS) database. We employed CiteSpace V to conduct the bibliometric study. A total of 915 articles or reviews were obtained from the WoS database. The number of publications has increased over the last two decades. The USA was the most productive among countries or regions in the field. According to the burst key words, neuroinflammation, hippocampus, safety, and modulation were the hot global research issues in the domain. Publications about NP associated with depression or anxiety have remarkably increased from 2000 to 2020. These historical opinions about NP associated with depression or anxiety could be an important practical basis for further research into potential development trends.
Learn More >The vagus nerve (VN), also called the pneumogastric nerve, connects the brainstem to organs contained in the chest and abdomen. Physiologically, VN stimulation can rapidly affect cardiac activity and heart rate (HR). VN neuropathy can increase the risk of arrhythmias and sudden death. Therefore, a selective test of VN function may be very useful. Since peripheral neurodynamic tests (NDT) are reliable for the assessment of neuropathies in somatic nerves, we aimed to validate a novel NDT to assess VN activity, namely, the VN-NTD.
Learn More >Pain Among an Inpatient Complex Chronic Care Population of Residents with and without Missing Limbs.
Limb loss occurs for various reasons (trauma, infection, vascular diseases, tumors, congenital absence). Limb loss is known to result in several types of pain. Little is known about pain in residents with missing limbs admitted to complex chronic care (CCC) facilities. This study examined the presence of pain and its intensity in CCC residents with and without missing limbs.
Learn More >The interleukin-22 cytokine (IL-22) has demonstrated efficacy in preclinical colitis models with non-immunosuppressive mechanism of action. Efmarodocokin alfa (UTTR1147A) is a fusion protein agonist that links IL-22 to the crystallisable fragment (Fc) of human IgG for improved pharmacokinetic characteristics, but with a mutation to minimise Fc effector functions.
Learn More >Up to a quarter of the world's population experience chronic pain, which, in addition to interfering with daily activities and waking function, is often associated with poor sleep. Individuals experiencing poor sleep are often encouraged to implement sleep hygiene strategies. However, current sleep hygiene strategies have not been developed considering the unique challenges faced by individuals with chronic pain and therefore they might not be as effective in this population. The aim of this scoping review is to map the state of the existing literature examining sleep hygiene strategies in individuals with chronic pain.
Learn More >Personalised management of neuropathic pain is an unmet clinical need due to heterogeneity of the underlying aetiologies, incompletely understood pathophysiological mechanisms, and limited efficacy of existing treatments. Recent studies on microRNA in pain preclinical models have begun to yield insights into pain-related mechanisms, identifying nociception-related species differences and pinpointing potential drug candidates. With the aim of bridging the translational gap towards the clinic, we generated a human pain-related integrative miRNA and mRNA molecular profile of the epidermis, the tissue hosting small nerve fibres, in a deeply phenotyped cohort of patients with sodium channel-related painful neuropathy not responding to currently available therapies. We identified four miRNAs strongly discriminating patients from healthy individuals, confirming their effect on differentially expressed gene-targets driving peripheral sensory transduction, transmission, modulation, and post-transcriptional modifications, with strong effects on gene targets including NEDD4. We identified a complex epidermal miRNA-mRNA network based on tissue-specific experimental data suggesting a cross-talk between epidermal cells and axons in neuropathy pain. Using immunofluorescence assay and confocal microscopy, we observed that Nav1.7 signal intensity in keratinocytes strongly inversely correlated with NEDD4 expression that was downregulated by miR-30 family, suggesting post-transcriptional fine tuning of pain-related protein expression. Our targeted molecular profiling advances the understanding of specific neuropathic pain fine signatures and may accelerate process towards personalised medicine in patients with neuropathic pain.
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