ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Delayed activation of spinal microglia contributes to the maintenance of bone cancer pain in female Wistar rats via P2X7 receptor and IL-18.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- P2X7 receptor as a key player in pathological pain: insights into Neuropathic, inflammatory, and cancer pain.Frontiers in pharmacology · 2025Pooled it
- Single-cell RNA sequencing analysis of bone cancer pain model induced by Lewis lung cancer cells in male mice.Annals of medicine · 2026Article
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Review
- M2 macrophage-secreted exosomal miR-216a regulates microglial polarization by targeting the HMGB1/TLR4/NF-κB pathway to alleviate bone cancer pain.American journal of translational research · 2026Article
- Central Sensitization and Nociplastic Pain: Shared Mechanisms in Fibromyalgia, Osteoarthritis, and Inflammatory Arthritis.Journal of pain research · 2026Review
- Fibroblast Growth Factor 8 Suppresses Neurotoxic Astrocytes and Alleviates Neuropathic Pain via Spinal FGFR3 Signaling.Neuroscience bulletin · 2025Article
- EXPRESS: Dehydrocorydaline can be a suitable candidate for analgesic purposes: a review on the current preclinical evidence.Molecular pain · 2025Review
- Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.Purinergic signalling · 2025Review
- The Circadian Clock Component REV-ERB Is an Analgesic Target for Cancer-Induced Tactile Pain Hypersensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Sex Differences in the Regulation of Interleukins in Chronic Pain: A Widely Recognized but Difficult-to-Tackle Factor.International journal of molecular sciences · 2025Review
- Review
- NFAT1 Signaling Contributes to Bone Cancer Pain by Regulating IL-18 Expression in Spinal Microglia.CNS neuroscience & therapeutics · 2025Article
- Mechanisms of Cancer-Induced Bone Pain.Journal of pain research · 2025Review
- Spinal astrocyte-derived interleukin-17A promotes pain hypersensitivity in bone cancer mice.Acta pharmaceutica Sinica. B · 2024Article
- Piperine attenuates cancer-associated pain induced by microglial activation via increasing miR-150-50p.Aging · 2024Article
- Systemic administration of Resolvin D1 reduces cancer-induced bone pain in mice: Lack of sex dependency in pain development and analgesia.Cancer medicine · 2024Article
- Discovery of a CCR2-targeting pepducin therapy for chronic pain.Pharmacological research · 2024Article
- Peripheral Mechanism of Cancer-Induced Bone Pain.Neuroscience bulletin · 2024Review
- Article
50 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence suggests that activation of spinal microglia contributes to the development of inflammatory and neuropathic pain. However, the role of spinal microglia in the maintenance of chronic pain remains controversial. Bone cancer pain shares features of inflammatory and neuropathic pain, but the temporal activation of microglia and astrocytes in this model is not well defined. Here, we report an unconventional role of spinal microglia in the maintenance of advanced-phase bone cancer pain in a female rat model. Bone cancer elicited delayed and persistent microglial activation in the spinal dorsal horn on days 14 and 21, but not on day 7. In contrast, bone cancer induced rapid and persistent astrocytic activation on days 7-21. Spinal inhibition of microglia by minocycline at 14 d effectively reduced bone cancer-induced allodynia and hyperalgesia. However, pretreatment of minocycline in the first week did not affect the development of cancer pain. Bone cancer increased ATP levels in CSF, and upregulated P2X7 receptor, phosphorylated p38, and IL-18 in spinal microglia. Spinal inhibition of P2X7/p-38/IL-18 pathway reduced advanced-phase bone cancer pain and suppressed hyperactivity of spinal wide dynamic range (WDR) neurons. IL-18 induced allodynia and hyperalgesia after intrathecal injection, elicited mechanical hyperactivity of WDR neurons in vivo, and increased the frequency of mEPSCs in spinal lamina IIo nociceptive synapses in spinal cord slices. Together, our findings demonstrate a novel role of microglia in maintaining advanced phase cancer pain in females via producing the proinflammatory cytokine IL-18 to enhance synaptic transmission of spinal cord nociceptive neurons.
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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.