Pain MechanismResearch PaperActivation of Gi induces mechanical hyperalgesia poststress or inflammation
Section snippets
Animals
Male (220–450 g) Sprague–Dawley rats (Charles River, Hollister, CA, USA) used in these experiments were housed in the Laboratory Animal Resource Center of the University of California, San Francisco, under a 12-h light/dark cycle. All experimental protocols were approved by the University of California, San Francisco, Institutional Animal Care and Use Committee, and conformed to NIH guidelines for the care and use of experimental animals. Effort was made to limit the numbers of animals used and
Results
While, for sound stress, we have previously shown a switch to Gi-as well as development of PKCε-dependence following recovery from prior inflammation we have not previously evaluated the switch to Gi dependence. In animals that had experienced prior inflammation at the site of nociceptive testing, PGE2 induced mechanical hyperalgesia was still unattenuated 4 h later (Fig. 1), a signature of hyperalgesic priming. This hyperalgesia was completely reversed by injection of PTx (100 ng/μl) at the
Discussion
In the present study we evaluated the role of the “inhibitory” heterotrimeric G protein, Gi, in inflammatory mediator-induced mechanical hyperalgesia in the rat. We have implicated a switch in signaling, from Gs to Gi, and onset of PKCε dependence for the second messenger pathway mediating PGE2-induced mechanical hyperalgesia, induced by prior stress (Khasar et al., 2008) or inflammation (Fig. 1; Aley et al., 2000). In the present study we evaluated whether activation of Gi was sufficient to
Conclusion
In conclusion, the present experiments confirm the role of a Gi-PKCε-mediated signaling pathway in primary afferent nociceptor sensitization and mechanical hyperalgesia associated with prior stress and inflammation, that may occur at or below the level of the Gi heterotrimeric G protein in the second messenger signaling pathway. It also provides support for a change in signaling pathway, a switch that is activated by stress or prior inflammation. Thus, Gi activity is sufficient for reproducing,
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