Acute Inflammatory Response via Neutrophil Activation Protects Against the Development of Chronic Pain
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE177034 | GEO | 2022/04/21
REPOSITORIES: GEO
Similar Datasets
Project description:Background & Aims: Irritable bowel syndrome (IBS) is a disorder characterized by chronic abdominal pain and is linked to post-inflammatory and stress-correlated factors that cause changes in the perception of visceral events. Increased evidence indicates that probiotic bacteria may be useful in treating IBS. Our aims were to evaluate the efficacy of treatment with VSL#3, a mixture of 8 probiotic bacteria strains, in the neonatal maternal separation (NMS)-induced visceral hypersensitivity rat model and to determine whether it modulates the colonic expression of pain-related genes. Methods: Male NMS pups were treated orally with placebo or VSL#3 at days 3-60, while normal, not separated rats were used as control. After 60 days from birth, perception of painful sensation induced by colorectal distension (CRD) was measured by assessing the abdominal withdrawal reflex (score 0-4). The colonic gene expression analysis was assessed by using Agilent Whole Rat Genome Oligo Microarrays. Results: NMS rats exhibited both hyperalgesia and allodynia when compared with controls. VSL#3 showed a potent analgesic effect on CRD-induced pain without modifying colorectal compliance. The microarray analysis demonstrated that NMS rats had both over- and downregulation of several genes involved in inflammatory and painful processes and VSL#3 was able to counteract these alterations. Conclusions: This study indicates that VSL#3 is effective in reducing visceral pain in an experimental model of IBS by induction or suppression of pain-modulating genes. These observations provide support for the use of VSL#3 in the treatment of painful conditions related to IBS. The dataset comprises 12 samples divided into three sample groups each representing a certain treatment condition of male rats.
2013-06-26 | E-GEOD-38942 | biostudies-arrayexpress
Project description:Acute Inflammatory Response via Neutrophil Activation Protects Against the Development of Chronic Pain
| PRJNA736882 | ENA
Project description:Background & Aims: Irritable bowel syndrome (IBS) is a disorder characterized by chronic abdominal pain and is linked to post-inflammatory and stress-correlated factors that cause changes in the perception of visceral events. Increased evidence indicates that probiotic bacteria may be useful in treating IBS. Our aims were to evaluate the efficacy of treatment with VSL#3, a mixture of 8 probiotic bacteria strains, in the neonatal maternal separation (NMS)-induced visceral hypersensitivity rat model and to determine whether it modulates the colonic expression of pain-related genes. Methods: Male NMS pups were treated orally with placebo or VSL#3 at days 3-60, while normal, not separated rats were used as control. After 60 days from birth, perception of painful sensation induced by colorectal distension (CRD) was measured by assessing the abdominal withdrawal reflex (score 0-4). The colonic gene expression analysis was assessed by using Agilent Whole Rat Genome Oligo Microarrays. Results: NMS rats exhibited both hyperalgesia and allodynia when compared with controls. VSL#3 showed a potent analgesic effect on CRD-induced pain without modifying colorectal compliance. The microarray analysis demonstrated that NMS rats had both over- and downregulation of several genes involved in inflammatory and painful processes and VSL#3 was able to counteract these alterations. Conclusions: This study indicates that VSL#3 is effective in reducing visceral pain in an experimental model of IBS by induction or suppression of pain-modulating genes. These observations provide support for the use of VSL#3 in the treatment of painful conditions related to IBS.
2013-06-26 | GSE38942 | GEO
Project description:Not all patients with nerve injury develop neuropathic pain. The extent of nerve damage and age at the time of injury are two of the few risk factors identified to date. In addition, preclinical studies show that neuropathic pain variance is heritable. To define such factors further, we performed a large-scale gene profiling experiment which plotted global expression changes in the rat dorsal root ganglion in three peripheral neuropathic pain models. This resulted in the discovery that the potassium channel alpha subunit KCNS1, involved in neuronal excitability, is constitutively expressed in sensory neurons and markedly downregulated following nerve injury. KCNS1 was then characterized by an unbiased network analysis as a putative pain gene, a result confirmed by single nucleotide polymorphism association studies in humans. A common amino acid changing allele, the 'valine risk allele', was significantly associated with higher pain scores in five of six independent patient cohorts assayed (total of 1359 subjects). Risk allele prevalence is high, with 18-22% of the population homozygous, and an additional 50% heterozygous. At lower levels of nerve damage (lumbar back pain with disc herniation) association with greater pain outcome in homozygote patients is P = 0.003, increasing to P = 0.0001 for higher levels of nerve injury (limb amputation). The combined P-value for pain association in all six cohorts tested is 1.14 E-08. The risk profile of this marker is additive: two copies confer the most, one intermediate and none the least risk. Relative degrees of enhanced risk vary between cohorts, but for patients with lumbar back pain, they range between 2- and 3-fold. Although work still remains to define the potential role of this protein in the pathogenic process, here we present the KCNS1 allele rs734784 as one of the first prognostic indicators of chronic pain risk. Screening for this allele could help define those individuals prone to a transition to persistent pain, and thus requiring therapeutic strategies or lifestyle changes that minimize nerve injury. Microarrays were run on mRNA extracted from adult rat L4 and L5 DRGs cells after 3,7,21,40 hours after three different sciatic nerve lesions [Spared Nerve Injury (SNI); Chronic Constriction Injury (CCI); Spinal Nerve Ligation (Ch) with Sham controls (SH)].
2011-07-14 | E-GEOD-30691 | biostudies-arrayexpress
Project description:Neurophysiological and transcriptomic predictors of chronic low back pain: towards precision pain management (NEAT Study)
| PRJNA671156 | ENA
Project description:Chronic pain is a debilitating and poorly-treated condition. The mechanisms underlying the development of chronic pain are not well understood. Nerve injury and inflammation cause alterations in gene expression in tissues associated with transmission of pain, supporting molecular and cellular mechanisms that maintain painful states. Previous studies in animal models and human patients suffering from different chronic pain conditions have examined changes in transcriptome associated with chronic pain. However, in most studies, the analyses were restricted to a single tissue or pain condition. In the current study, we performed next-generation sequencing of dorsal root ganglia, spinal cord, brain and blood in mouse models of nerve injury and inflammation-induced chronic pain. Comparative analyses of differentially expressed genes (DEG) across these tissues in two pain models identified the extracellular matrix organization (ECMO) pathway as the most commonly affected pathway. Interestingly, examination of GWAS datasets revealed an over-representation of DEGs within the ECMO pathway in SNPs most strongly associated with human back pain. Remarkably, manipulation of the extracellular matrix in the mouse significantly affected the development of pain hypersensitivity following nerve injury, supporting our gene expression findings. In summary, our comprehensive analysis of transcriptional landscape across different mouse pain models and tissues as well as human GWAS datasets identified extracellular matrix organization as a central molecular pathway in the development of chronic pain.
2019-04-04 | GSE111216 | GEO
Project description:The transition from acute to chronic pain is critically important but not well understood. Here, we investigated the pathophysiological mechanisms underlying the transition from acute to chronic low back pain (LBP) and performed transcriptome-wide analysis in peripheral immune cells of 98 participants with acute LBP, followed for 3 months. Transcriptomic changes were compared between patients whose LBP was resolved at 3 months with those whose LBP persisted. We found thousands of dynamic transcriptional changes over 3 months in LBP participants with resolved pain but none in those with persistent pain. Transient neutrophil-driven up-regulation of inflammatory responses was protective against the transition to chronic pain. In mouse pain assays, early treatment with a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led to prolonged pain despite being analgesic in the short term; such a prolongation was not observed with other analgesics. Depletion of neutrophils delayed resolution of pain in mice, whereas peripheral injection of neutrophils themselves, or S100A8/A9 proteins normally released by neutrophils, prevented the development of long-lasting pain induced by an anti-inflammatory drug. Analysis of pain trajectories of human subjects reporting acute back pain in the UK Biobank identified elevated risk of pain persistence for subjects taking NSAIDs. Thus, despite analgesic efficacy at early time points, the management of acute inflammation may be counterproductive for long-term outcomes of LBP sufferers.
| S-EPMC10317000 | biostudies-literature
Project description:Genomics of Pain - Resilience to Pain
| PRJNA498368 | ENA
Project description:Genomics of Pain - Resilience to Pain
| PRJNA498369 | ENA
Project description:Chronic pain is associated with persistent but reversible structural and functional changes in prefrontal cortex (PFC). This stable yet malleable plasticity implicates epigenetic mechanisms, including DNA methylation, as a potential mediator of chronic pain-induced changes. We have previously demonstrated that chronic oral administration of the methyl donor S-adenosyl methionine (SAM) is capable of attenuating long-term peripheral neuropathic pain and affecting global PFC DNA methylation. However, there was no evidence as of yet that alterations in DNA methylation underlie SAM-mediated pain attenuation. To elucidate these mechanisms, we performed epigenome-wide analysis of mouse PFC after 4 months of SAM treatment initiated 3 months following induction of peripheral nerve injury. Over injury triggered chronic pain was associated with 4000 differentially methylated genomic regions which were enriched in intracellular signaling, cell locomotion and migration, cytoskeletal structure, and cell adhesion pathways. A third of the regions that were differentially methylated in chronic pain mice (1415 regions representing 1030 genes) were reversed by SAM treatment. 100 genes with known pain-related function were differentially methylated following nerve injury; several of which were reversed by SAM treatment. These results demonstrate that DNA methylation alterations in the PFC caused by chronic pain and reversed by SAM treatment providing at least partially a mechanism of action. These data point to the possibility of epigenetic modulators such as SAM as novel approach to treat chronic pain.
2020-11-24 | GSE162016 | GEO