The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Morphine activates neuroinflammation in a manner parallel to endotoxin
Open accessAbstract
Opioids create a neuroinflammatory response within the CNS, compromising opioid-induced analgesia and contributing to various unwanted actions. How this occurs is unknown but has been assumed to be via classic opioid receptors. Herein, we provide direct evidence that morphine creates neuroinflammation via the activation of an innate immune receptor and not via classic opioid receptors. We demonstrate that morphine binds to an accessory protein of Toll-like receptor 4 (TLR4), myeloid differentiation protein 2 (MD-2), thereby inducing TLR4 oligomerization and triggering proinflammation. Small-molecule inhibitors, RNA interference, and genetic knockout validate the TLR4/MD-2 complex as a feasible target for beneficially modifying morphine actions. Disrupting TLR4/MD-2 protein–protein association potentiated morphine analgesia in vivo and abolished morphine-induced proinflammation in vitro, the latter demonstrating that morphine-induced proinflammation only depends on TLR4, despite the presence of opioid receptors. These results provide an exciting, nonconventional avenue to improving the clinical efficacy of opioids.
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Inflammaging: a new immune–metabolic viewpoint for age-related diseases
Franceschi, C., Garagnani, P., Parini, P., Giuliani, C., & Santoro, A. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0059-4 · Cited by 3,586
Pathological pain and the neuroimmune interface
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Self-citationNeurobiology of opioid addiction: Opponent process, hyperkatifeia, and negative reinforcement
Koob, G. F. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.023 · Cited by 477
Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis
Ferrini, F., Trang, T., Mattioli, T.-A. M., Laffray, S., Del'Guidice, T., Lorenzo, L.-E., Castonguay, A., Doyon, N., Zhang, W., Godin, A. G., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3295 · Cited by 437
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Metadata
- Authors
- Wang, X., Loram, L. C., Ramos, K., de Jesus, A. J., Thomas, J., Cheng, K., Reddy, A., Somogyi, A. A., Hutchinson, M. R., Watkins, L. R., & Yin, H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2012-04-02
- Volume
- 109
- Issue
- 16
- Pages
- 6325-6330
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1988795126
- Cited by
- 517
- References
- 33
- FWCI
- 20.57
- Type
- journal article
- Language
- en
- Open access
- green
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