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. Author manuscript; available in PMC: 2015 Nov 30.
Published in final edited form as: Prog Mol Biol Transl Sci. 2015 Jan 30;131:409–434. doi: 10.1016/bs.pmbts.2014.11.010

Figure 4. The role of aPKCs and BDNF in hyperalgesic priming initiation and maintenance.

Figure 4

Nociceptor activation leads to spinal BDNF release and a postsynaptic mTORC1-dependent translation of aPKC protein. These newly synthesized aPKCs are then phosphorylated by PDK1. Increased levels and phosphorylation of aPKCs are thought to be involved in initiating priming. Once priming is established (right panel), increased aPKC protein and phosphorylation leads to a constitutive increase in AMPAR trafficking to the postsynaptic membrane. This appears to be regulated by BDNF signaling via trkB with BDNF potentially being released from postsynaptic dendrites in the maintenance stage of priming. Presynaptic trkB may also be activated by increased BDNF action in primed animals. Once established, hyperalgesic priming can be permanently reversed by inhibition of aPKCs with ZIP, disruption of AMPAR trafficking with pep2M or via inhibition of trkB/BDNF signaling with ANA-12 or trkB-Fc, respectively.