Bio: Xinran Hou is an academic researcher from Central South University. The author has contributed to research in topics: Medicine & Materials science. The author has an hindex of 3, co-authored 5 publications receiving 40 citations.
TL;DR: Intrathecal application of trichostatin A (TSA), a classic pan-HDAC inhibitor, ameliorated tactile hypersensitivity and enhanced the analgesic effect of morphine in BCP rats, probably by restoring MOR expression in spinal cord.
TL;DR: It is demonstrated that HDAC2 in spinal cord contributed to the mechanical hyperalgesia in BCP rats, and this effect may be associated with KCC2 modulation, a vital mechanism of many types of pathological pain.
TL;DR: This research confirmed that HDAC2 was involved in mechanical and thermal hyperalgesia induced by peripheral nerve injury and found two essential participants in neuropathic pain in the inhibitory circuit of the central nervous system: GAD65 and KCC2 were increased in the spinal cord of CCI rats afterHDAC2 knockdown.
Abstract: Neuropathic pain is a worldwide health concern with poor treatment outcomes. Accumulating evidence suggests that histone hypoacetylation is involved in development and maintenance of neuropathic pain. Thus, many natural and synthetic histone deacetylase (HDACs) inhibitors were tested and exhibited a remarkable analgesic effect against neuropathic pain in animals. However, studies evaluating specific subtypes of HDACs contributing to neuropathic pain are limited. In this study, using the chronic constriction injury (CCI) rat model, we found that mRNA and protein levels of HDAC2 were increased in the lumbar spinal cord of rats after sciatic nerve injury. Intrathecal injection of TSA, a pan-HDAC inhibitor, suppressed the increase in HDAC2 protein but not mRNA, and showed a dose-dependent pain-relieving effect. By introducing HDAC2-specific shRNA into the spinal cord via a lentivirus vector, we confirmed that HDAC2 mediates mechanical and thermal hyperalgesia after nerve injury. Further examination found two essential participants in neuropathic pain in the inhibitory circuit of the central nervous system: GAD65 and KCC2 were increased in the spinal cord of CCI rats after HDAC2 knockdown. Thus, our research confirmed that HDAC2 was involved in mechanical and thermal hyperalgesia induced by peripheral nerve injury. Furthermore, GAD65 and KCC2 were the possible downstream targets of HDAC2 in pain modulation pathways.
TL;DR: In this article , a flexible carbon nanofiber membrane with a three-dimensional network structure was fabricated based on PMDA/ODA polyimide by combining electrospinning, imidization, and carbonization strategies.
Abstract: Free-standing and flexible carbon nanofiber membranes (CNMs) with a three-dimensional network structure were fabricated based on PMDA/ODA polyimide by combining electrospinning, imidization, and carbonization strategies. The influence of carbonization temperature on the physical-chemical characteristics of CNMs was investigated in detail. The electrochemical performances of CNMs as free-standing electrodes without any binder or conducting materials for lithium-ion batteries were also discussed. Furthermore, the surface state and internal carbon structure had an important effect on the nitrogen state, electrical conductivity, and wettability of CNMs, and then further affected the electrochemical performances. The CNMs/Li metal half-cells exhibited a satisfying charge–discharge cycle performance and excellent rate performance. They showed that the reversible specific capacity of CNMs carbonized at 700 °C could reach as high as 430 mA h g−1 at 50 mA g−1, and the value of the specific capacity remained at 206 mA h g−1 after 500 cycles at a high current density of 1 A g−1. Overall, the newly developed carbon nanofiber membranes will be a promising candidate for flexible electrodes used in high-power lithium-ion batteries, supercapacitors and sodium-ion batteries.
TL;DR: This study provided a landscape of dysregulated lncRNA and mRNA in spinal cord of bone cancer pain and detected novel potential targets for treatment in the future.
Abstract: Bone cancer pain (BCP) is one of the most common types of chronic cancer pain and its pathogenesis has not been fully understood. Long non-coding RNAs (lncRNAs) are new promising targets in the field of pain research, however, their involvements in BCP have not been reported. In the present study, we established the BCP model by implantation of Walker 256 carcinoma cells into rats’ tibial medullary cavity and performed transcriptome sequencing of the ipsilateral lumbar spinal cord to explore changes in expression profiles of lncRNA and mRNA. We identified 1220 differently expressed mRNAs (DEmRNAs) (1171 up-regulated and 49 down-regulated) and 323 differently expressed lncRNAs (DElncRNAs) (246 up-regulated and 77 down-regulated) in BCP model, among which 10 DEmRNAs (5 up-regulated and 5 down-regulated) and 10 DElncRNAs (5 up-regulated and 5 down-regulated) were validated the expression by RT-qPCR. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on the expression of DEmRNAs and DElncRNAs, showing that they were mainly enriched in inflammatory and immunologic processes/pathways. Finally, we constructed a co-expression network and a ceRNA network of DEmRNAs and DElncRNAs to exhibit a potential regulatory mechanism of DElncRNAs, directly regulating protein coding gene expression in cis or in trans and indirectly regulating protein coding gene expression by sponging miRNA. In conclusion, our study provided a landscape of dysregulated lncRNA and mRNA in spinal cord of bone cancer pain and detected novel potential targets for treatment in the future.
TL;DR: How a new classification of chronic cancer-related pain in ICD-11 is intended to help develop more individualized management plans for cancer patients and to stimulate research into these pain syndromes is described.
Abstract: Worldwide, the prevalence of cancer is rising and so too is the number of patients who survive their cancer for many years thanks to the therapeutic successes of modern oncology. One of the most frequent and disabling symptoms of cancer is pain. In addition to the pain caused by the cancer, cancer treatment may also lead to chronic pain. Despite its importance, chronic cancer-related pain is not represented in the current International Classification of Diseases (ICD-10). This article describes the new classification of chronic cancer-related pain for ICD-11. Chronic cancer-related pain is defined as chronic pain caused by the primary cancer itself or metastases (chronic cancer pain) or its treatment (chronic postcancer treatment pain). It should be distinguished from pain caused by comorbid disease. Pain management regimens for terminally ill cancer patients have been elaborated by the World Health Organization and other international bodies. An important clinical challenge is the longer term pain management in cancer patients and cancer survivors, where chronic pain from cancer, its treatment, and unrelated causes may be concurrent. This article describes how a new classification of chronic cancer-related pain in ICD-11 is intended to help develop more individualized management plans for these patients and to stimulate research into these pain syndromes.
TL;DR: A review of epigenetic changes, including histone modifications, DNA methylation, non-coding RNAs, and alteration of chromatin modifiers, that have been shown to trigger modification of nociception after neural lesions to find novel targets for chronic neuropathic pain treatment.
Abstract: Accumulating evidence suggests that epigenetic alterations lie behind the induction and maintenance of neuropathic pain. Neuropathic pain is usually a chronic condition caused by a lesion, or pathological change, within the nervous system. Neuropathic pain appears frequently after nerve and spinal cord injuries or diseases, producing a debilitation of the patient and a decrease of the quality of life. At the cellular level, neuropathic pain is the result of neuronal plasticity shaped by an increase in the sensitivity and excitability of sensory neurons of the central and peripheral nervous system. One of the mechanisms thought to contribute to hyperexcitability and therefore to the ontogeny of neuropathic pain is the altered expression, trafficking, and functioning of receptors and ion channels expressed by primary sensory neurons. Besides, neuronal and glial cells, such as microglia and astrocytes, together with blood borne macrophages, play a critical role in the induction and maintenance of neuropathic pain by releasing powerful neuromodulators such as pro-inflammatory cytokines and chemokines, which enhance neuronal excitability. Altered gene expression of neuronal receptors, ion channels, and pro-inflammatory cytokines and chemokines, have been associated to epigenetic adaptations of the injured tissue. Within this review, we discuss the involvement of these epigenetic changes, including histone modifications, DNA methylation, non-coding RNAs, and alteration of chromatin modifiers, that have been shown to trigger modification of nociception after neural lesions. In particular, the function on these processes of EZH2, JMJD3, MeCP2, several histone deacetylases (HDACs) and histone acetyl transferases (HATs), G9a, DNMT, REST and diverse non-coding RNAs, are described. Despite the effort on developing new therapies, current treatments have only produced limited relief of this pain in a portion of patients. Thus, the present review pretends to contribute to find novel targets for chronic neuropathic pain treatment.
TL;DR: The data suggest that fecal transplantation from lean to obese, insulin-resistant mice decreases obesity-induced hypersensitivity and increases nerve density in the skin, and circulating butyrate, a metabolite secreted by gut microbiome and absorbed in the blood stream, underlies some of the effects of FMT.
Abstract: Obesity affects over 2 billion people worldwide and is accompanied by peripheral neuropathy (PN) and an associated poorer quality of life. Despite high prevalence, the molecular mechanisms underlying the painful manifestations of PN are poorly understood, and therapies are restricted to use of painkillers or other drugs that do not address the underlying disease. Studies have demonstrated that the gut microbiome is linked to metabolic health and its alteration is associated with many diseases, including obesity. Pathologic changes to the gut microbiome have recently been linked to somatosensory pain, but any relationships between gut microbiome and PN in obesity have yet to be explored. Our data show that mice fed a Western diet developed indices of PN that were attenuated by concurrent fecal microbiome transplantation (FMT). In addition, we observed changes in expression of genes involved in lipid metabolism and calcium handling in cells of the peripheral nerve system (PNS). FMT also induced changes in the immune cell populations of the PNS. There was a correlation between an increase in the circulating short-chain fatty acid butyrate and pain improvement following FMT. Additionally, butyrate modulated gene expression and immune cells in the PNS. Circulating butyrate was also negatively correlated with distal pain in 29 participants with varied body mass index. Our data suggest that the metabolite butyrate, secreted by the gut microbiome, underlies some of the effects of FMT. Targeting the gut microbiome, butyrate, and its consequences may represent novel viable approaches to prevent or relieve obesity-associated neuropathies.
TL;DR: Results indicated that miR-26a-5p might serve as a potential therapeutic target for neuropathic pain through targeting MAPK6, which indicated thatMiR- 26a- 5p could act as a negative regulator of neuropathicPain development through targetingMAPK6.
TL;DR: It is reported that downregulation of tyrosine phosphatase STEP61 links disinhibition to NMDAR potentiation in human and rodent spinal pain processing, and an ex vivo human preclinical model is developed to help bridge the translational divide.
Abstract: Dysregulated excitability within the spinal dorsal horn is a critical mediator of chronic pain. In the rodent nerve injury model of neuropathic pain, BDNF-mediated loss of inhibition (disinhibition) gates the potentiation of excitatory GluN2B N-methyl-d-aspartate receptor (NMDAR) responses at lamina I dorsal horn synapses. However, the centrality of this mechanism across pain states and species, as well as the molecular linker involved, remain unknown. Here, we show that KCC2-dependent disinhibition is coupled to increased GluN2B-mediated synaptic NMDAR responses in a rodent model of inflammatory pain, with an associated downregulation of the tyrosine phosphatase STEP61. The decreased activity of STEP61 is both necessary and sufficient to prime subsequent phosphorylation and potentiation of GluN2B NMDAR by BDNF at lamina I synapses. Blocking disinhibition reversed the downregulation of STEP61 as well as inflammation-mediated behavioural hypersensitivity. For the first time, we characterize GluN2B-mediated NMDAR responses at human lamina I synapses and show that a human ex vivo BDNF model of pathological pain processing downregulates KCC2 and STEP61 and upregulates phosphorylated GluN2B at dorsal horn synapses. Our results demonstrate that STEP61 is the molecular brake that is lost following KCC2-dependent disinhibition and that the decrease in STEP61 activity drives the potentiation of excitatory GluN2B NMDAR responses in rodent and human models of pathological pain. The ex vivo human BDNF model may thus form a translational bridge between rodents and humans for identification and validation of novel molecular pain targets.