Fig. 6. Schematic diagram of proposed synaptic circuitry. In the dorsal horn, norepinephrine is released by terminals of noradrenergic neurons located in pontine nuclei onto “GABAergic” neurons at both the soma and the dendrites and axon terminals. Activation of postsynaptic α¹receptors at somatodendritic sites depolarizes the GABAergic neuron sufficient to generate an orthodromic action potential. This action potential invades presynaptic axon terminals and causes coordinated release of γ-aminobutyric acid (GABA), which in turn produces the observed large-amplitude inhibitory postsynaptic currents (IPSCs) in substantia gelatinosa (SG) neurons. Activation of presynaptic α¹receptors at axon terminals also facilitates the release of GABA from presynaptic terminals of GABAergic neurons. GABA-evoked currents hyperpolarize SG interneurons, thereby making generation of an action potential in response to nociceptive primary-afferent inputs less likely. This decrease in SG interneuron firing is consistent with the loss of polysynaptic, but not monosynaptic EPSPs, in lamina IV–V neurons after dorsal root stimulation.