The DOI matches its Crossref record; 87 of the 87 references it cites were found in a registry or an index.
Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation
Open accessAbstract
Significance: Pain after disease/damage of the nervous system is predominantly treated with opioids, but without exploration of the long-term consequences. We demonstrate that a short course of morphine after nerve injury doubles the duration of neuropathic pain. Using genetic and pharmacological interventions, and innovative Designer Receptor Exclusively Activated by Designer Drugs disruption of microglia reactivity, we demonstrate that opioid-prolonged neuropathic pain arises from spinal microglia and NOD-like receptor protein 3 inflammasome formation/activation. Inhibiting these processes permanently resets amplified pain to basal levels, an effect not previously reported. These data support the “two-hit hypothesis” of amplification of microglial activation—nerve injury being the first “hit,” morphine the second. The implications of such potent microglial “priming” has fundamental clinical implications for pain and may extend to many chronic neurological disorders.
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 46,426
Quantitative assessment of tactile allodynia in the rat paw
Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., & Yaksh, T. L. (1994) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(94)90144-9 · Cited by 7,697
Dose translation from animal to human studies revisited.
Reagan‐Shaw, S., Nihal, M., & Ahmad, N. (2008) · The FASEB Journal · doi:10.1096/fj.07-9574lsf · Cited by 6,524
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Bennett, G. J., & Xie, Y.-K. (1988) · Pain · doi:10.1016/0304-3959(88)90209-6 · Cited by 5,376
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Hargreaves, K., Dubner, R., Brown, F., Flores, C., & Joris, J. (1988) · Pain · doi:10.1016/0304-3959(88)90026-7 · Cited by 5,135
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Activation and regulation of the inflammasomes
Latz, E., Xiao, T. S., & Stutz, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3452 · Cited by 2,884
Opiate Receptor: Demonstration in Nervous Tissue
Pert, C. B., & Snyder, S. H. (1973) · Science · doi:10.1126/science.179.4077.1011 · Cited by 2,388
Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S., & Roth, B. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700293104 · Cited by 2,046
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Neuroinflammation and Central Sensitization in Chronic and Widespread Pain
Ji, R.-R., Nackley, A., Huh, Y., Terrando, N., & Maixner, W. (2018) · Anesthesiology · doi:10.1097/aln.0000000000002130 · Cited by 1,630
Pain regulation by non-neuronal cells and inflammation
Ji, R.-R., Chamessian, A., & Zhang, Y.-Q. (2016) · Science · doi:10.1126/science.aaf8924 · Cited by 1,314
Self-citationMicroglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential
Inoue, K., & Tsuda, M. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.2 · Cited by 908
Liu, Z., Yao, X., Jiang, W., Li, W., Zhu, S., Liao, C., Zou, L., Ding, R., & Chen, J. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01751-2 · Cited by 430
Systemic inflammation impairs microglial Aβ clearance through NLRP3 inflammasome
Tejera, D., Mercan, D., Sanchez‐Caro, J. M., Hanan, M., Greenberg, D., Soreq, H., Latz, E., Golenbock, D., & Heneka, M. T. (2019) · The EMBO Journal · doi:10.15252/embj.2018101064 · Cited by 351
Metadata
- Authors
- Grace, P. M., Strand, K. A., Galer, E. L., Urban, D. J., Wang, X., Baratta, M. V., Fabisiak, T. J., Anderson, N. D., Cheng, K., Greene, L. I., Berkelhammer, D., Zhang, Y., Ellis, A. L., Yin, H. H., Campeau, S., Rice, K. C., Roth, B. L., Maier, S. F., & Watkins, L. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2016-05-31
- Volume
- 113
- Issue
- 24
- Pages
- E3441-50
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2409306902
- Cited by
- 367
- References
- 87
- FWCI
- 26.69
- Type
- journal article
- Language
- en
- Open access
- green
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- Grace, P. M., Strand, K. A., Galer, E. L., Urban, D. J., Wang, X., Baratta, M. V., Fabisiak, T. J., Anderson, N. D., Cheng, K., Greene, L. I., Berkelhammer, D., Zhang, Y., Ellis, A. L., Yin, H. H., Campeau, S., Rice, K. C., Roth, B. L., Maier, S. F., & Watkins, L. R. (2016). Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1602070113
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