ArticleThe Journal of clinical investigation2022
mTORC2 mediates structural plasticity in distal nociceptive endings that contributes to pain hypersensitivity following inflammation.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- The role of mTORC2/RICTOR in immune cells and inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- The Genetic Architecture of Chronic Cough: From Sensory Hypersensitivity to Treatable Trait.Pulmonary therapy · 2026Review
- Development and External Validation of a Nomogram for Predicting Postherpetic Neuralgia Risk in Patients with Herpes Zoster: A Retrospective Cohort Study.Journal of pain research · 2026Article
- IGF-1R promotes pain-like behavior in rats with myofascial pain syndrome via the PI3K/AKT pathway.Scientific reports · 2025Article
- Review
- Early positive tactile stimulation reverses the increase of anxiety and decrease of sociality induced by early chronic mechanical pain in mandarin voles.Integrative zoology · 2025Article
- Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Targeting spinal mechanistic target of rapamycin complex 2 alleviates inflammatory and neuropathic pain.Brain : a journal of neurology · 2025Article
- Sustained nerve growth factor-induced C-nociceptor sensitization to electrical sinusoidal stimulation in humans.Pain reports · 2024Article
- Hydrogen Sulfide can Scavenge Free Radicals to Improve Spinal Cord Injury by Inhibiting the p38MAPK/mTOR/NF-κB Signaling Pathway.Neuromolecular medicine · 2024Review
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Immune drivers of physiological and pathological pain.The Journal of experimental medicine · 2024Article
- Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain.Military Medical Research · 2024Article
- Scratching increases epidermal neuronal branching and alters psychophysical testing responses in atopic dermatitis and brachioradial pruritus.Frontiers in molecular neuroscience · 2023Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 6 countries.
Funding
Abstract
The encoding of noxious stimuli into action potential firing is largely mediated by nociceptive free nerve endings. Tissue inflammation, by changing the intrinsic properties of the nociceptive endings, leads to nociceptive hyperexcitability and thus to the development of inflammatory pain. Here, we showed that tissue inflammation-induced activation of the mammalian target of rapamycin complex 2 (mTORC2) triggers changes in the architecture of nociceptive terminals and leads to inflammatory pain. Pharmacological activation of mTORC2 induced elongation and branching of nociceptor peripheral endings and caused long-lasting pain hypersensitivity. Conversely, nociceptor-specific deletion of the mTORC2 regulatory protein rapamycin-insensitive companion of mTOR (Rictor) prevented inflammation-induced elongation and branching of cutaneous nociceptive fibers and attenuated inflammatory pain hypersensitivity. Computational modeling demonstrated that mTORC2-mediated structural changes in the nociceptive terminal tree are sufficient to increase the excitability of nociceptors. Targeting mTORC2 using a single injection of antisense oligonucleotide against Rictor provided long-lasting alleviation of inflammatory pain hypersensitivity. Collectively, we showed that tissue inflammation-induced activation of mTORC2 causes structural plasticity of nociceptive free nerve endings in the epidermis and inflammatory hyperalgesia, representing a therapeutic target for inflammatory pain.
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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.