ArticleTranslational perioperative and pain medicine
Intrathecal rapamycin attenuates morphine-induced analgesic tolerance and hyperalgesia in rats with neuropathic pain.
Article in Translational perioperative and pain medicine. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Focal Adhesion Kinase Inhibition Ameliorates Burn Injury-Induced Chronic Pain in Rats.Molecular neurobiology · 2025Article
- A Single Injection of rAAV-shmTOR in Peripheral Nerve Persistently Attenuates Nerve Injury-Induced Mechanical Allodynia.International journal of molecular sciences · 2023Article
- Intrathecal administration of the fat-mass and obesity-associated protein inhibitor mitigates neuropathic pain in female rats.Translational perioperative and pain medicine · 2022Article
- Effect of Pharmacological Inhibition of Fat-Mass and Obesity-Associated Protein on Nerve Trauma-Induced Pain Hypersensitivities.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Electro-acupuncture Suppresses AXL Expression in Dorsal Root Ganglion Neurons and Enhances Analgesic Effect of AXL Inhibitor in Spinal Nerve Ligation Induced-Neuropathic Pain Rats.Neurochemical research · 2021Article
- β-endorphin at the intersection of pain and cancer progression: Preclinical evidence.Neuroscience letters · 2021Article
- NAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Effects of glucosamine against morphine-induced antinociceptive tolerance and dependence in mice.Journal of biomedical science · 2019Article
- Systemic Rapamycin Attenuates Morphine-Induced Analgesic Tolerance and Hyperalgesia in Mice.Neurochemical research · 2019Article
- The Contribution of the Descending Pain Modulatory Pathway in Opioid Tolerance.Frontiers in neuroscience · 2018Article
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- MiR-30b Attenuates Neuropathic Pain by Regulating Voltage-Gated Sodium Channel Nav1.3 in Rats.Frontiers in molecular neuroscience · 2017Article
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Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Repeated and long-term administration of opioids is often accompanied by the initiation of opioid-induced analgesic tolerance and hyperalgesia in chronic pain patients. Our previous studies showed that repeated intrathecal morphine injection activated the mammalian target of rapamycin complex 1 (mTORC1) in spinal dorsal horn neurons and that blocking this activation prevented the initiation of morphine-induced tolerance and hyperalgesia in healthy rats. However, whether spinal mTORC1 is required for morphine-induced tolerance and hyperalgesia under neuropathic pain conditions remains elusive. We here observed the effect of intrathecal infusion of rapamycin, a specific mTORC1 inhibitor, on morphine-induced tolerance and hyperalgesia in a neuropathic pain model in rats induced by the fifth lumbar spinal nerve ligation (SNL). Continuous intrathecal infusion of morphine for one week starting on day 8 post-SNL led to morphine tolerance demonstrated by morphine-induced reduction in maximal possible analgesic effect (MPAE) to tail heat stimuli and ipsilateral paw withdrawal threshold (PWT) to mechanical stimuli in SNL rats. Such reduction was attenuated by co-infusion of rapamycin. Co-infusion of rapamycin also blocked morphine tolerance demonstrated by attenuation of morphine-induced reduction in MPAE in sham rats and morphine-induced hyperalgesia demonstrated by the reverse of morphine-induced reduction in PWT on both sides of sham rats and on the contralateral side of SNL rats. The results suggest that mTORC1 inhibitors could serve as promising medications for use as adjuvants with opioids in clinical neuropathic pain management.
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Identifiers
26339682PMC4556423W2412213312What 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.