ArticleMolecular pain
Neuroinflammation and central PI3K/Akt/mTOR signal pathway contribute to bone cancer pain.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Bone metastasis and pain research through the dual lens of bibliometrics and bioinformatics: knowledge structure, frontiers, and core pathway analysis (2015-2024).Frontiers in medicine · 2025Pooled it
- Molecular targets in bone cancer pain: a systematic review of inflammatory cytokines.Journal of molecular medicine (Berlin, Germany) · 2024Pooled it
- Epidermal growth factor receptor signaling modulates postoperative pain and inflammatory responses.Frontiers in immunology · 2026Review
- IGF-1R promotes pain-like behavior in rats with myofascial pain syndrome via the PI3K/AKT pathway.Scientific reports · 2025Article
- Cancer pain: molecular mechanisms and management.Molecular biomedicine · 2025Review
- Spinal Involvement of TRPV1 and PI3K/AKT/mTOR Pathway During Chronic Postoperative Pain in Mice.Brain sciences · 2025Article
- Cellular senescence in the innervated niche modulates cancer-associated pain: an emerging therapeutic target?Frontiers in immunology · 2025Review
- Pharmacological Perspective on the Neurobiology of PI3K-Akt-mTOR Signalling in Opioid Dependence.CNS & neurological disorders drug targets · 2025Review
- Liu-Shen-Wan inhibits PI3K/Akt and TRPV1 signaling alleviating bone cancer pain in rats.Cancer biology & therapy · 2024Article
- From pain to tumor immunity: influence of peripheral sensory neurons in cancer.Frontiers in immunology · 2024Review
- Ibrutinib Delays ALS Installation and Increases Survival of SOD1Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Roles of hypoxic environment and M2 macrophage-derived extracellular vesicles on the progression of non-small cell lung cancer.BMC pulmonary medicine · 2023Article
- Recent advances to Neuroprotection: repurposing drugs against neuroinflammatory disorders.Molecular biology reports · 2023Review
- Altered expression of inflammation-associated molecules in striatum: an implication for sensitivity to heavy ion radiations.Frontiers in cellular neuroscience · 2023Article
- Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.Cancers · 2022Review
- STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex.Cancers · 2022Article
- Dual PI3Kδ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Hydrogen Sulfide Inhibits Inflammatory Pain and Enhances the Analgesic Properties of Delta Opioid Receptors.Antioxidants (Basel, Switzerland) · 2021Article
- MiR-135-5p Alleviates Bone Cancer Pain by Regulating Astrocyte-Mediated Neuroinflammation in Spinal Cord through JAK2/STAT3 Signaling Pathway.Molecular neurobiology · 2021Article
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPain is one of the most common and distressing symptoms suffered by patients with progression of cancer; however, the mechanisms responsible for hyperalgesia are not well understood. Since the midbrain periaqueductal gray is an important component of the descending inhibitory pathway controlling on central pain transmission, in this study, we examined the role for pro-inflammatory cytokines of the periaqueductal gray in regulating mechanical and thermal hyperalgesia evoked by bone cancer via phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signals.
methodsBreast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats to induce mechanical and thermal hyperalgesia. Western blot analysis and ELISA were used to examine PI3K/protein kinase B (Akt)/mTOR and pro-inflammatory cytokine receptors and the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α).
resultsProtein expression levels of p-PI3K/p-Akt/p-mTOR were amplified in the periaqueductal gray of bone cancer rats, and blocking PI3K-mTOR pathways in the periaqueductal gray attenuated hyperalgesia responses. In addition, IL-1β, IL-6, and TNF-α were elevated in the periaqueductal gray of bone cancer rats, and expression of their respective receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor (TNFR) subtype TNFR1) was upregulated. Inhibition of IL-1R, IL-6R, and TNFR1 alleviated mechanical and thermal hyperalgesia in bone cancer rats, accompanied with downregulated PI3K-mTOR.
conclusionsOur data suggest that upregulation of pro-inflammatory cytokine signal in the periaqueductal gray of cancer rats amplifies PI3K-mTOR signal in this brain region and alters the descending pathways in regulating pain transmission, and this thereby contributes to the development of bone cancer-induced pain.
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