Gene expression profiles from multimodal patch-seq neuron samples of the pig dorsal root ganglion
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE263466 | GEO | 2026/01/25
REPOSITORIES: GEO
Similar Datasets
Project description:Here we show that importin alpha (α) 3 (KPNA4) controls pain responsiveness in peripheral sensory neurons. An importin α3 knockout mouse showed reduced responsiveness to noxious heat or chemical pain, as well as greater tolerance to neuropathic pain. Similar findings were obtained upon acute knockdown of importin α3 in peripheral sensory neurons. Transcriptome analyses and immunohistochemistry indicated that importin α 3 deficient neurons were impaired in nuclear import of c-Fos. Forty days after spared nerve injury acute down-regulation of importin α3, c-FOS, Jun and the dominat negative AAV9 viruses rescue the neuropathic pain phenotype. In silico screens identified importin α3 deficiency mimicking drug leads that attenuated neuropathic pain and reduced c-Fos nuclear localization. Hence, perturbing c-Fos nuclear import by importin α3 can provide analgesia at peripheral loci in the nervous system
2020-08-17 | GSE137515 | GEO
Project description:Nerve injury-induced changes in gene expression in primary sensory neurons, such as trigeminal ganglion (TG) neurons, play a critical role in the genesis of neuropathic pain. Therefore, understanding the molecular mechanisms underlying these changes in the TGs following peripheral nerve injury will enable us to develop a new avenue for managing trigeminal-mediated neuropathic pain. Studies have highlighted the involvement of miRNA-mediated modulation in a wide range of diseases, leading to the exploration of miRNA-based therapeutics as a potential treatment strategy. Here, in this RNA-seq database, we have found that microRNA-216a-3p (miR-216a-3p) and miR-32-5p (miR-32-5p), which are downregulated in injured TGs, are novel functional RNAs involved in regulating trigeminal-mediated neuropathic pain. Histone methylation-mediated miRNA downregulation in TG neurons regulates trigeminal neuropathic pain by targeting either STIM1 (H3K27me3/SOX10/miR-216a-3p/STIM1) or Cav3.2 (GR/miR-32-5p/Cav3.2) channels. Moreover, we found that miR-323-3p exhibited the most significant upregulation in the injured TG. Understanding the mechanistic role of the PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons may advance the discovery of novel therapeutic strategies for neuropathic pain.
2025-01-08 | GSE192803 | GEO
Project description:Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein synthesis; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found mTOR activation in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. Combining transcriptomic profiling, electrophysiological recording and pharmacologic manipulations, we demonstrated that activated mTOR promoted neuropeptide Y (NPY) induction in mechanoreceptors and that NPY acted on Y2 receptors (Y2R) but not Y1R to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented its function. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.
2022-09-01 | GSE184014 | GEO
Project description:Neuropathic pain is a highly prevalent condition for which treatments are hampered by low efficacy and dose-limiting side-effects. Injury to the somatosensory nervous system causes maladaptive plasticity that initiates and maintains chronic pain. Emerging evidence suggests that inflammatory cells of the innate immune system shape the injured nervous system and drive pain pathogenesis. Data from preclinical models and human patient biopsies have specifically implicated peripheral macrophage populations for a pro-algesic role, yet how these cell types influence damaged sensory neurons and whether they directly sensitise their neuronal activity is unclear. Here, we have developed an iPSC co-culture system to study the interactions of macrophages and sensory neurons in a fully humanised experimental model. We found that analogous to endogenous counterparts, iPSC-derived macrophages (iMacs) display a dynamic molecular and functional profile that is highly dependent on neuronal context. Co-culture with injured iPSC-derived sensory neurons (iSNs) induces morphological, gene expression, and secretory profile changes in iMacs that are consistent with in vivo nerve injury datasets. iMacs in turn amplify spontaneous firing in damaged sensory neurons, implicating macrophages in a cardinal feature of neuropathic pain. These results illustrate the utility of an iPSC-based model to study signalling between these two cell types; they support a role for macrophages in directly amplifying damaged sensory neuron activity and highlight disrupting pathological signalling between these cell types as a promising strategy for future analgesic drug development.
2025-05-28 | GSE298326 | GEO
Project description:Neuropathic pain is a highly prevalent condition for which treatments are hampered by low efficacy and dose-limiting side-effects. Injury to the somatosensory nervous system causes maladaptive plasticity that initiates and maintains chronic pain. Emerging evidence suggests that inflammatory cells of the innate immune system shape the injured nervous system and drive pain pathogenesis. Data from preclinical models and human patient biopsies have specifically implicated peripheral macrophage populations for a pro-algesic role, yet how these cell types influence damaged sensory neurons and whether they directly sensitise their neuronal activity is unclear. Here, we have developed an iPSC co-culture system to study the interactions of macrophages and sensory neurons in a fully humanised experimental model. We found that analogous to endogenous counterparts, iPSC-derived macrophages (iMacs) display a dynamic molecular and functional profile that is highly dependent on neuronal context. Co-culture with injured iPSC-derived sensory neurons (iSNs) induces morphological, gene expression, and secretory profile changes in iMacs that are consistent with in vivo nerve injury datasets. iMacs in turn amplify spontaneous firing in damage sensory neurons, implicating macrophages in a cardinal feature of neuropathic pain. These results illustrate the utility of an iPSC-based model to study signalling between these two cell types; supporting a role for macrophages in directly amplifying damaged sensory neuron activity and suggesting that disrupting pathological signalling between these cell types could be a fruitful avenue for analgesic drug development.
2025-05-28 | GSE298325 | GEO
Project description:Peripheral nerve injury alters the expression of hundreds of proteins in dorsal root ganglia (DRG). Targeting some of these proteins has led to successful treatments for acute pain, but not for sustained postoperative neuropathic pain. The latter may require targeting multiple proteins. Since a single microRNA (miR) can affect the expression of multiple proteins, here, we describe an approach to identify chronic neuropathic pain-relevant miRs. We used two variants of the spared nerve injury (SNI): Sural-SNI and Tibial-SNI and found distinct pain phenotypes between the two. Both models induced strong mechanical allodynia, but only Sural-SNI rats maintained strong mechanical and cold allodynia, as previously reported. In contrast, we found that Tibial-SNI rats recovered from mechanical allodynia and never developed cold allodynia. Since both models involve nerve injury, we increased the probability of identifying differentially regulated miRs that correlated with the quality and magnitude of neuropathic pain and decreased the probability of detecting miRs that are solely involved in neuronal regeneration. We found seven such miRs in L3-L5 DRG. The expression of these miRs increased in Tibial-SNI. These miRs displayed a lower level of expression in Sural-SNI, with four having levels lower than those in sham animals. Bioinformatics analysis of how these miRs could affect the expression of some ion channels supports the view that, following a peripheral nerve injury, the increase of the 7 miRs may contribute to the recovery from neuropathic pain while the decrease of four of them may contribute to the development of chronic neuropathic pain. The approach used resulted in the identification of a small number of potentially neuropathic pain relevant miRs. Additional studies are required to investigate whether manipulating the expression of the identified miRs in primary sensory neurons can prevent or ameliorate chronic neuropathic pain following peripheral nerve injuries. To identify the miRs that were differentially dysregulated between Tibial-SNI and Sural-SNI, we first performed 12 microarrays in a limited number of samples (in four individual DRGs per group: Sham, Tibial-SNI and Sural-SNI; two L3-DRG and two L4-DRG). Then, miRs identified as having differential expression were corroborated with real time qRT-PCR in RNA isolated from individual DRGs (L3, L4 and L5) derived from 4 rats per group (not presented here, but in the manuscript).
2014-09-29 | E-GEOD-60033 | biostudies-arrayexpress
Project description:Our perception of pain changes according to expectation, context and mood illustrating how top-down-circuits affect sensory processing. Here we developed an intersectional platform for identifying supraspinal descending neurons that are engaged when an animal experiences pain. Amongst these, we identified a cluster of cells in the pontine micturition center (Barrington’s nucleus), expressing corticotropin-releasing-hormone (BarCrh) that detect painful but not innocuous stimuli. When activated, BarCrh-neurons attenuate nocifensive responses as well as tactile neuropathic pain. Mechanistically, pain related input from the ventrolateral periaqueductal gray activates BarCrh-neurons, which in turn project to the spinal dorsal horn to mediate analgesia. In combination, our data demonstrate that Barrington’s nucleus is not just a relay station dedicated to triggering micturition but also powerfully controls painful sensory input to the brain.
2025-02-17 | GSE237054 | GEO
Project description:Purpose: Nerve injury-induced hyperactivity of primary sensory neurons in the dorsal root ganglion (DRG) contributes critically to chronic pain development, but its underlying mechanisms remain incompletely understood. Chronic neuropathic pain has a clear epigenetic component, however, most studies so far have focused on histone modifications. We determined changes of DNA methylation in the rat DRG, spinal cord, and prefrontal cortex after spinal nerve ligation (SNL).
2018-07-05 | GSE114865 | GEO
Project description:Purpose: Nerve injury-induced hyperactivity of primary sensory neurons in the dorsal root ganglion (DRG) contributes critically to chronic pain development, but its underlying mechanisms remain incompletely understood. Chronic neuropathic pain has a clear epigenetic component, however, most studies so far have focused on histone modifications. We determined changes of DNA methylation in the rat DRG, spinal cord, and prefrontal cortex after spinal nerve ligation (SNL).
2018-06-29 | GSE100641 | GEO
Project description:Mesenchymal stromal cells (MSC) have emerged as a promising therapeutic option for neuropathic pain (NP), but the mechanisms remain elusive. Using murine pain models, we demonstrated that MSC effectively alleviate pain, with efficacy comparable to dexmedetomidine, a moderate analgesic. Mechanistically, peripheral delivery of MSC activated pulmonary Npy2r-expressing vagal sensory neurons, which project to the nucleus tractus solitarius and ventral lateral periaqueductal gray area, driving analgesia via the vagal lung-to-brain pathway. Chemogenetic activation of Npy2r sensory neurons similarly ameliorated spared nerve injury (SNI)-induced mechanical allodynia and thermal hyperalgesia. Furthermore, we found that MSC-derived extracellular ATP, released via pannexin1, activated Npy2r sensory neurons through purinergic receptor P2X2 (P2rx2). Strikingly, inhalation of a P2rx2 agonist produced significant therapeutic effects in SNI mice. Together, our findings reveal that Npy2r sensory neuron-mediated lung-brain axis underlies MSC-induced analgesia and highlight the potential of targeting body-brain pathways for novel NP treatments.
2025-08-18 | GSE305716 | GEO