The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain
Abstract
The P2X(7) purinoceptor is a ligand-gated cation channel, expressed predominantly by cells of immune origin, with a unique phenotype which includes release of biologically active inflammatory cytokine, interleukin (IL)-1beta following activation, and unique ion channel biophysics observed only in this receptor family. Here we demonstrate that in mice lacking this receptor, inflammatory (in an adjuvant-induced model) and neuropathic (in a partial nerve ligation model) hypersensitivity is completely absent to both mechanical and thermal stimuli, whilst normal nociceptive processing is preserved. The knockout animals were unimpaired in their ability to produce mRNA for pro-IL-1beta, and cytometric analysis of paw and systemic cytokines from knockout and wild-type animals following adjuvant insult suggests a selective effect of the gene deletion on release of IL-1beta and IL-10, with systemic reductions in adjuvant-induced increases in IL-6 and MCP-1. In addition, we show that this receptor is upregulated in human dorsal root ganglia and injured nerves obtained from chronic neuropathic pain patients. We hypothesise that the P2X(7) receptor, via regulation of mature IL-1beta production, plays a common upstream transductional role in the development of pain of neuropathic and inflammatory origin. Drugs which block this target may have the potential to deliver broad-spectrum analgesia.
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Cites
Parvathenani, L. K., Tertyshnikova, S., Greco, C. R., Roberts, S. B., Robertson, B., & Posmantur, R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209478200 · Cited by 488
Reanalysis of P2X7Receptor Expression in Rodent Brain
Sim, J. A., Young, M. T., Sung, H.-Y., North, R. A., & Surprenant, A. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1469-04.2004 · Cited by 264
Colomar, A., Marty, V., Médina, C., Combe, C., Parnet, P., & Amédée, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304534200 · Cited by 103
Cited by
Cellular and Molecular Mechanisms of Pain
Basbaum, A. I., Bautista, D. M., Scherrer, G., & Julius, D. (2009) · Cell · doi:10.1016/j.cell.2009.09.028 · Cited by 4,344
Immunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466
Principles of early drug discovery
Hughes, J., Rees, S., Kalindjian, S., & Philpott, K. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01127.x · Cited by 2,859
Self-citationThe P2X7 Receptor in Infection and Inflammation
Di Virgilio, F., Dal Ben, D., Sarti, A. C., Giuliani, A. L., & Falzoni, S. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.020 · Cited by 1,267
Role of the Immune system in chronic pain
Marchand, F., Perretti, M., & McMahon, S. B. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1700 · Cited by 1,098
Metadata
- Authors
- Chessell, I. P., Hatcher, J. P., Bountra, C., Michel, A. D., Hughes, J. P., Green, P., Egerton, J., Murfin, M., Richardson, J., Peck, W. L., Grahames, C. B. A., Casula, M. A., Yiangou, Y., Birch, R., Anand, P., & Buell, G. N.
- Venue
- Pain
- Published
- 2005-04
- Volume
- 114
- Issue
- 3
- Pages
- 386-396
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2056148352
- Cited by
- 789
- References
- 3
- FWCI
- 26.28
- Type
- journal article
- Language
- en
- Open access
- closed
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- Chessell, I. P., Hatcher, J. P., Bountra, C., Michel, A. D., Hughes, J. P., Green, P., Egerton, J., Murfin, M., Richardson, J., Peck, W. L., Grahames, C. B. A., Casula, M. A., Yiangou, Y., Birch, R., Anand, P., & Buell, G. N. (2005). Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain. https://doi.org/10.1016/j.pain.2005.01.002
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