Figure 3: Schematic of TNFα induced potentiation of spinal cord synaptic transmission. Microglial release of TNFα increases excitatory neurotransmission in the dorsal horn via both presynaptic and postsynaptic mechanisms. At presynaptic sites, TNFα increases glutamate release via TRPV1 activation and there will be a subsequent increase in intracellular Ca2+. At postsynaptic sites, TNFα increases the activity of AMPA and NMDA receptors via activation of PI3 K and ERK on glutamatergic neurons to increase excitatory drive.