ArticleThe Journal of clinical investigation2018
Reducing CXCR4-mediated nociceptor hyperexcitability reverses painful diabetic neuropathy.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 89 citations in OpenAlex.
- Skin-resident Langerhans cells drive neuropathic pain via chemokine-dependent neuron-immune communication.The Journal of clinical investigation · 2026Article
- Lidocaine alleviates diabetic neuropathic pain by inhibiting spinal astrocyte activation through modulation of the CXCL13/CXCR5 axis.Journal of molecular histology · 2026Article
- Human pain transcriptomics: lessons learned so far.Pain reports · 2026Review
- OBESITY-INDUCED ENDOTHELIAL FENESTRATION AND CAPILLARY LEAKAGE CONTRIBUTE TO INCREASED PAIN SENSATION.bioRxiv : the preprint server for biology · 2026Article
- Dorsal Root Ganglion as a Hub for Peripheral Sensitization: A Hierarchical Regulation Model and Translational Progress.Journal of pain research · 2026Review
- CXCL13/CXCR5: a new target for pain treatment.International journal of surgery (London, England) · 2025Review
- The polygenic architecture of hidradenitis suppurativa reveals signaling mechanisms that implicate epithelial remodeling.medRxiv : the preprint server for health sciences · 2025Article
- Local keratinocyte-nociceptor interactions enhance obesity-mediated painful small fiber neuropathy via NGF-TrkA-PI3K signaling axis.iScience · 2025Article
- The CXCL12/CXCR4 Axis: An Emerging Therapeutic Target for Chronic Pain.Journal of pain research · 2025Review
- The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion.International journal of molecular sciences · 2024Article
- Elevated plasma CXCL12 leads to pain chronicity via positive feedback upregulation of CXCL12/CXCR4 axis in pain synapses.The journal of headache and pain · 2024Article
- Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models.EMBO reports · 2024Article
- Keratinocyte-Derived Exosomes in Painful Diabetic Neuropathy.bioRxiv : the preprint server for biology · 2024Article
- Unraveling impact and potential mechanisms of baseline pain on efficacy of immunotherapy in lung cancer patients: a retrospective and bioinformatic analysis.Frontiers in immunology · 2024Article
- Novel drugs affecting diabetic peripheral neuropathy.Iranian journal of basic medical sciences · 2024Review
- Misregulation of mitochondria-lysosome contact dynamics in Charcot-Marie-Tooth Type 2B disease Rab7 mutant sensory peripheral neurons.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Up-regulation of microglial chemokine CXCL12 in anterior cingulate cortex mediates neuropathic pain in diabetic mice.Acta pharmacologica Sinica · 2023Article
- Article
- Review
- Neuropathic pain; what we know and what we should do about it.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Painful diabetic neuropathy (PDN) is an intractable complication of diabetes that affects 25% of patients. PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. We hypothesize that chemokine CXCL12/CXCR4 signaling is central to this mechanism, as we have shown that CXCL12/CXCR4 signaling is necessary for the development of mechanical allodynia, a pain hypersensitivity behavior common in PDN. Focusing on DRG neurons expressing the sodium channel Nav1.8, we applied transgenic, electrophysiological, imaging, and chemogenetic techniques to test this hypothesis. In the high-fat diet mouse model of PDN, we were able to prevent and reverse mechanical allodynia and small-fiber degeneration by limiting CXCR4 signaling or neuronal excitability. This study reveals that excitatory CXCR4/CXCL12 signaling in Nav1.8-positive DRG neurons plays a critical role in the pathogenesis of mechanical allodynia and small-fiber degeneration in a mouse model of PDN. Hence, we propose that targeting CXCR4-mediated DRG nociceptor hyperexcitability is a promising therapeutic approach for disease-modifying treatments for this currently intractable and widespread affliction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.