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. Author manuscript; available in PMC: 2013 Mar 6.
Published in final edited form as: FEBS J. 2011 Dec 5;279(1):2–11. doi: 10.1111/j.1742-4658.2011.08390.x

Figure 1.

Figure 1

A model for the role of sensitization of nociceptive dorsal horn neuron in pain hypersensitivity. Left; under basal conditions NMDAR activity is suppressed by partial blockade of the channel by Mg2+ and by the activity of the protein tyrosine phosphatase, STEP, and the kinase, Csk. KAIR, kainate receptor. Middle; nociceptive input increases NMDAR-mediated currents by 1) relief of Mg2+ inhibition, 2) by activation of Src (Src*) via the actions of PTPa and activated CAKβ (CAKβ-P) which overcomes the suppression by STEP, and 3) by sensitizing the NMDARs to raised intracellular [Na+]. Right; upregulation of NMDAR function allows a large boost in entry of Ca2+, which binds to calmodulin (CaM) causing activation of CaMKII, not illustrated. The enhancement of glutamatergic transmission is ultimately expressed through increased numbers of AMPA/KAIRs in the postsynaptic membrane and/or enhanced AMPA/KAIR activity.