Chronic hyperalgesic priming in the rat involves a novel interaction between cAMP and PKCepsilon second messenger pathways
- PMID: 15621379
- DOI: 10.1016/j.pain.2004.10.021
Chronic hyperalgesic priming in the rat involves a novel interaction between cAMP and PKCepsilon second messenger pathways
Erratum in
- Pain. 2005 May;115(1-2):223
Abstract
Toward the goal of defining new pharmacological targets for the treatment of chronic pain conditions, in previous studies we established a model, termed 'hyperalgesic priming,' in which an acute inflammatory stimulus causes a long-lasting latent susceptibility to hyperalgesia induced by subsequent exposures to the inflammatory mediator, prostaglandin E2 (PGE2). Those investigations suggested the hypothesis that priming induces a novel linkage between the PGE2-activated second messenger cascade and the epsilon isoform of protein kinase C (PKCepsilon). In the present study, comparison of dose-response relations for hyperalgesia produced by PGE2, forskolin, 8-Br-cAMP, or the protein kinase A (PKA) catalytic subunit, in primed versus normal animals, demonstrated that priming-induced enhancement of the PGE2-activated second messenger cascade occurs downstream to adenylate cyclase and upstream to PKA. Therefore, PGE2-induced hyperalgesia in the primed animal is enhanced by the recruitment of a novel cAMP/PKCepsilon signaling pathway in addition to the usual cAMP/PKA pathway. These observations suggest that pharmacological disruption of the novel interaction between cAMP and PKCepsilon might provide a route toward the development of highly specific methods to reverse cellular processes that underlie chronic pain states.
Similar articles
-
Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming.J Neurosci. 2015 Apr 15;35(15):6107-16. doi: 10.1523/JNEUROSCI.5085-14.2015. J Neurosci. 2015. PMID: 25878283 Free PMC article.
-
Transient attenuation of protein kinase Cepsilon can terminate a chronic hyperalgesic state in the rat.Neuroscience. 2003;120(1):219-26. doi: 10.1016/s0306-4522(03)00267-7. Neuroscience. 2003. PMID: 12849754
-
Further confirmation of the role of adenyl cyclase and of cAMP-dependent protein kinase in primary afferent hyperalgesia.Neuroscience. 1991;44(1):131-5. doi: 10.1016/0306-4522(91)90255-m. Neuroscience. 1991. PMID: 1722888
-
Critical role of nociceptor plasticity in chronic pain.Trends Neurosci. 2009 Dec;32(12):611-8. doi: 10.1016/j.tins.2009.07.007. Epub 2009 Sep 24. Trends Neurosci. 2009. PMID: 19781793 Free PMC article. Review.
-
Hyperalgesic Priming in the Transition From Acute to Chronic Pain: Focus on Different Models and the Molecular Mechanisms Involved.J Pain Res. 2025 Mar 21;18:1491-1501. doi: 10.2147/JPR.S514851. eCollection 2025. J Pain Res. 2025. PMID: 40135188 Free PMC article. Review.
Cited by
-
Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming.J Neurosci. 2015 Apr 15;35(15):6107-16. doi: 10.1523/JNEUROSCI.5085-14.2015. J Neurosci. 2015. PMID: 25878283 Free PMC article.
-
Cyclic nucleotide signaling in sensory neuron hyperexcitability and chronic pain after nerve injury.Neurobiol Pain. 2019 Mar 8;6:100028. doi: 10.1016/j.ynpai.2019.100028. eCollection 2019 Aug-Dec. Neurobiol Pain. 2019. PMID: 31223142 Free PMC article. Review.
-
Role of nociceptor αCaMKII in transition from acute to chronic pain (hyperalgesic priming) in male and female rats.J Neurosci. 2013 Jul 3;33(27):11002-11. doi: 10.1523/JNEUROSCI.1785-13.2013. J Neurosci. 2013. PMID: 23825405 Free PMC article.
-
Transient decrease in nociceptor GRK2 expression produces long-term enhancement in inflammatory pain.Neuroscience. 2012 Oct 11;222:392-403. doi: 10.1016/j.neuroscience.2012.07.004. Epub 2012 Jul 13. Neuroscience. 2012. PMID: 22796071 Free PMC article.
-
Marked Sexual Dimorphism in the Role of the Ryanodine Receptor in a Model of Pain Chronification in the Rat.Sci Rep. 2016 Aug 8;6:31221. doi: 10.1038/srep31221. Sci Rep. 2016. PMID: 27499186 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources