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Genome-wide analysis of dorsal root ganglion (DRG) gene expression after morphine or oxycodone treatment

ABSTRACT: Analyse of gene expression modification after chronic analgesic treatment. The hypothesis tested in the present study was that oxycodone and morphine induced gene expression modification. Results provide important information to understand the analgesic effects of oxycodone as compared to morphine in a neuropathic pain model

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE53897 | GEO | 2014/01/09

SECONDARY ACCESSION(S): PRJNA233659

REPOSITORIES: GEO

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Genome-wide analysis of dorsal root ganglion (DRG) gene expression after morphine or oxycodone treatment

Project description:Analyse of gene expression modification after chronic analgesic treatment. The hypothesis tested in the present study was that oxycodone and morphine induced gene expression modification. Results provide important information to understand the analgesic effects of oxycodone as compared to morphine in a neuropathic pain model Total RNA obtained from DRG of neuropathic or control animals after oxycodone or morphine treatment

2014-01-09 | E-GEOD-53897 | biostudies-arrayexpress

Oxycodone withdrawal induces HDAC1/2-dependent transcriptional maladaptations in the reward pathway in a murine model of peripheral nerve injury

Project description:The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. In this study, we developed a mouse model of oxycodone exposure to gain insight into genes and molecular pathways in reward-related brain regions that are affected by prolonged exposure to oxycodone and subsequent withdrawal in the presence or absence of chronic neuropathic pain. RNA-Sequencing (RNA-Seq) and bioinformatic analyses revealed that oxycodone withdrawal alone triggers robust gene expression adaptations in the nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and ventral tegmental area (VTA), with numerous genes and pathways selectively affected by oxycodone withdrawal under peripheral nerve injury states. Our pathway analysis predicted that histone deacetylase 1 (HDAC1), an epigenetic modifier with a prominent role in striatal plasticity, is a top upstream regulator in opioid withdrawal in both the NAc and mPFC. Indeed, treatment with the novel HDAC1/2 inhibitor RBC1HI (Regenacy Brain Class 1 HDAC Inhibitor) attenuated behavioral manifestations of oxycodone withdrawal, with the drug being more efficacious under states of neuropathic pain. Since RBC1HI displays antiallodynic actions in models of neuropathic pain, inhibition of HDAC1/2 may provide an avenue for chronic pain patients dependent on opioids to transition to non-opioid analgesics. Overall, our study highlights transcriptomic events in components of the reward circuitry associated with oxycodone withdrawal under pain-free and prolonged neuropathic pain states, thereby providing information on possible new targets for the treatment of physical dependence to opioids and transitioning individuals to non-opioid medications for chronic pain management.

2023-01-23 | GSE223541 | GEO

Analgesia of naloxone and morphine in wild-type and NY1DD sickle cell mice using BMAP cDNA microarrays

Project description:Sickle cell disease is the most common genetic disorder in African-Americans. The opioid analgesic, morphine, has long been the treatment for the severe pain associated with this disease. Here we reveal that the opioid antagonist, naloxone, possesses potent analgesic activity in two strains of sickle cell mice (NY1DD and hBERK1) and not in their respective controls (ICR-CD1 and C57BL/6J) when administered by three parenteral routes. In the NY1DD sickle mice, naloxone (i.c.v.) possessed ~300-fold greater potency than morphine (i.c.v.). Other opioid antagonists (naltrexone, norbinaltorphimine, naltrindole) were substantially less effective in producing analgesia. Naloxone and morphine were synergistic in NY1DD mice, suggesting that analgesia was mediated via different receptor systems. Since microarray analysis suggested naloxone-induced down-regulation of the CCR5 chemokine receptor in NY1DD mice but not in control mice, the role of its endogenous ligand, CCL5 (RANTES), was investigated. Keywords: Comparison of drug induced gene expression

2007-12-20 | GSE6479 | GEO

Morphine alleviates pain after heart cryonjury in zebrafish without impeding regeneration

Project description:Nociceptive response belongs to a basic animal behavior facilitating adaptability and survival upon external or internal stimuli. Fish, similarly to higher vertebrates, also possess nociceptive machinery. Current protocols involving procedures performed on adult zebrafish including heart cryoinjury do not, however, take into account the adverse effects including pain that may potentially arise from these methodologies. Here, we assess the effect of two analgesics, lidocaine and morphine, followed after the heart cryoinjury in zebrafish. Monitoring swimming behaviour together with histology and gene expression analysis at the single cell level using scRNA sequencing and RNAscope fluorescent in situ hybridization technology, we show morphine, but not lidocaine, significantly improves animal welfare 6 hours post-cryoinjury, without impairing heart regeneration process. Altogether, morphine should be considered as the analgesic of choice to reduce post-surgical pain in adult zebrafish.

2022-05-06 | GSE158919 | GEO

Effect of Neat1 knockdown on gene expression in the rat dorsal root ganglion (DRG) after spinal nerve ligation

Project description:To investigate the involvement of Neat1 in neuropathic pain, Neat1 was knocked down in DRG neurons by the injection of AAV vector encoding shRNA for Neat1.

2023-07-27 | GSE228730 | GEO

MicroRNA expression profiling of prefrontal cortex samples from C57 mice treated with saline or morphine

Project description:Our previous study showed that Dicer1 expression is positively correlated with the development of analgesic tolerance. To further understand the miRNA regulation by Dicer in the development of tolerance, we performed microRNA profiling using Agilent mouse miRNA arrays to identify the miRNA profiles in the prefrontal cortex from C57BL/6J (C57) mice under saline or morphine treatment.

2016-11-01 | GSE75893 | GEO

Morphine PVT TRAPSeq

Project description:Using an oral self-administration paradigm, we have seen morphine increase neural activity in the Paraventricular Nucleus of the Thalamus (PVT). Morphine binds primarily to Mu Opioid Receptors (MORs), which are highly expressed in the PVT. Translating Ribosome Affinity Purification (TRAP)-Sequencing was conducted on PVT neurons that express MORs

2022-10-04 | GSE214560 | GEO

HDAC inhibitors attenuate the development of hypersensitivity in models of neuropathic pain [DRG tissue]

Project description:Histone deacetylase inhibitors (HDACIs) interfere with the epigenetic process of histone acetylation and are known to have analgesic properties in models of chronic inflammatory pain. The aim of this study was to determine whether these compounds could also affect neuropathic pain. Different class I HDACIs were delivered intrathecally into rat spinal cord in models of traumatic nerve injury and antiretroviral drug-induced peripheral neuropathy (stavudine, d4T). Mechanical and thermal hypersensitivity was attenuated by 40% to 50% as a result of HDACI treatment, but only if started before any insult. The drugs globally increased histone acetylation in the spinal cord, but appeared to have no measurable effects in relevant dorsal root ganglia in this treatment paradigm, suggesting that any potential mechanism should be sought in the central nervous system. Microarray analysis of dorsal cord RNA revealed the signature of the specific compound used (MS-275) and suggested that its main effect was mediated through HDAC1. Taken together, these data support a role for histone acetylation in the emergence of neuropathic pain. n = 4, HDACi treated vs. vehicle treated. Injured ipsilateral DRG after L5 spinal nerve transection. Spinal cord tissue was run in a separate Affymetrix experiment.

2013-10-01 | E-GEOD-51295 | biostudies-arrayexpress

Spatial transcriptomics on human dorsal root ganglion (DRG)

Project description:Visium Spatial Gene Expression by the 10X genomics protocol was performed on 2 sections of human DRG tissue to elucidate the spatial transcriptomic organization.

2023-09-14 | GSE215994 | GEO

Epitranscriptomic map of N6-methyladenosine circular RNAs in the spinal cord of morphine-tolerant rats

Project description:Morphine tolerance is a tricky problem, the mechanism of it is still unclear. Circular RNAs (CircRNAs) play important roles in biological process of central nervous system. N6-methyladenosine (m6A) as a key post-transcriptional modification of RNA can regulate the metabolism and functions of circRNAs. Here we conducted this research to explore the patterns of m6A-methylation of circRNAs in the spinal cords of 4 morphine tolerated rats and 4 normal rats.

2022-04-05 | GSE199892 | GEO

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