The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis
Open accessAbstract
A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opiates. We found that hyperalgesia-inducing treatment with morphine resulted in downregulation of the K+-Cl− co-transporter KCC2, impairing Cl− homeostasis in rat spinal lamina l neurons. Restoring the anion equilibrium potential reversed the morphine-induced hyperalgesia without affecting tolerance. The hyperalgesia was also reversed by ablating spinal microglia. Morphine hyperalgesia, but not tolerance, required μ opioid receptor–dependent expression of P2X4 receptors (P2X4Rs) in microglia and μ-independent gating of the release of brain-derived neurotrophic factor (BDNF) by P2X4Rs. Blocking BDNF-TrkB signaling preserved Cl− homeostasis and reversed the hyperalgesia. Gene-targeted mice in which Bdnf was deleted from microglia did not develop hyperalgesia to morphine. However, neither morphine antinociception nor tolerance was affected in these mice. Our findings dissociate morphine-induced hyperalgesia from tolerance and suggest the microglia-to-neuron P2X4-BDNF-KCC2 pathway as a therapeutic target for preventing hyperalgesia without affecting morphine analgesia.
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BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain
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Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
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Ji, R.-R., Chamessian, A., & Zhang, Y.-Q. (2016) · Science · doi:10.1126/science.aaf8924 · Cited by 1,314
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Metadata
- Authors
- 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., Mohr, D., Beggs, S., Vandal, K., Beaulieu, J.-M., Cahill, C. M., Salter, M. W., & De Koninck, Y.
- Venue
- Nature Neuroscience
- Published
- 2013-01-06
- Volume
- 16
- Issue
- 2
- Pages
- 183-192
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2021440104
- Cited by
- 437
- References
- 59
- FWCI
- 27.13
- Type
- journal article
- Language
- en
- Open access
- green
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- 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., Mohr, D., Beggs, S., Vandal, K., Beaulieu, J.-M., Cahill, C. M., Salter, M. W., & De Koninck, Y. (2013). Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis. Nature Neuroscience. https://doi.org/10.1038/nn.3295
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