ArticleNeuroscience2010
Mammalian target of rapamycin in spinal cord neurons mediates hypersensitivity induced by peripheral inflammation.
Article in Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
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- Pleiotropic Effects of Metformin in Osteoarthritis.Life (Basel, Switzerland) · 2023Review
- The mTOR inhibitor rapamycin suppresses trigeminal neuropathic pain and p-MKK4/p-p38 mitogen-activated protein kinase-mediated microglial activation in the trigeminal nucleus caudalis of mice with infraorbital nerve injury.Frontiers in molecular neuroscience · 2023Article
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- Roles of AMPK and Its Downstream Signals in Pain Regulation.Life (Basel, Switzerland) · 2021Review
- Pharmacological Manipulation of Translation as a Therapeutic Target for Chronic Pain.Pharmacological reviews · 2021Review
- Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats.Molecular brain · 2020Article
- Persistent Rheb-induced mTORC1 activation in spinal cord neurons induces hypersensitivity in neuropathic pain.Cell death & disease · 2020Article
- Metformin: A Prospective Alternative for the Treatment of Chronic Pain.Frontiers in pharmacology · 2020Review
- Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats.Molecular neurobiology · 2019Article
- Suberoylanilide Hydroxamic Acid Triggers Autophagy by Influencing the mTOR Pathway in the Spinal Dorsal Horn in a Rat Neuropathic Pain Model.Neurochemical research · 2019Article
- Perspectives of RAS and RHEB GTPase Signaling Pathways in Regenerating Brain Neurons.International journal of molecular sciences · 2018Review
- Diosgenin Glucoside Protects against Spinal Cord Injury by Regulating Autophagy and Alleviating Apoptosis.International journal of molecular sciences · 2018Article
- BDNF Activates mTOR to Upregulate NR2B Expression in the Rostral Anterior Cingulate Cortex Required for Inflammatory Pain-Related Aversion in Rats.Neurochemical research · 2018Article
- Translational Control Mechanisms in Persistent Pain.Trends in neurosciences · 2018Review
- eIF4E-Dependent Translational Control: A Central Mechanism for Regulation of Pain Plasticity.Frontiers in genetics · 2018Review
- Sinomenine attenuates chronic inflammatory pain in mice.Metabolic brain disease · 2017Article
- Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury.Frontiers in molecular neuroscience · 2017Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
mTOR, the mammalian target of rapamycin, is a serine-threonine kinase known to regulate cell proliferation and growth. mTOR has also been implicated in neuronal synaptic plasticity as well as in pain transmission in models of chemically induced and neuropathic pain. To date, the role of mTOR as a modulator of inflammatory pain has not been examined. In this study, we investigated the role of mTOR in Sprague-Dawley rats using the carrageenan model of inflammatory pain. mRNA of Ras homolog enriched in brain (Rheb), a GTPase that positively regulates mTOR activation, was significantly increased 2 h following carrageenan injection. Four hours after induction of inflammation phosphorylation (p) of p70S6 kinase (S6K), ribosomal protein S6 (S6) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) was increased, indicating mTOR activation. Inhibition of spinal mTOR with intrathecal (i.t.) injection of rapamycin (0.1-3 microg) led to a dose-dependent decrease in carrageenan-induced thermal hyperalgesia and a reduction of mechanical allodynia. In vitro studies confirmed rapamycin inhibition of the mTOR pathway. Carrageenan-induced activation of the mTOR pathway in rats was localized predominantly to dorsal horn neurons in the superficial lamina. Taken together, these data show that the mTOR pathway is activated in dorsal horn neurons during inflammatory pain, and that inhibition of spinal mTOR attenuates inflammation-induced thermal and tactile hypersensitivity. Hence, our study indicates that spinal mTOR is an important regulator of spinal sensitization and suggests that targeting mTOR may provide a new avenue for pain therapy.
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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.