Figure 1.

Long-term potentiation and chronic pain. (a) Neurons in the anterior cingulate cortex (ACC) are believed to play critical roles in pain perception and chronic pain. In ACC pyramidal cells (see inset image for an example), pairing presynaptic stimulation with postsynaptic depolarization induces long-term increases in the amplitudes of AMPA receptor-mediated excitatory postsynaptic currents (EPSCs). Similar potentiation can be induced by theta burst stimulation (TBS) and spike-timing LTP induction protocols (adapted from Zhao et al. [6]). In the lower plot, it shows that strong TBS induced late phase LTP (L-LTP) in the ACC (red circles), and control pathways show stable responses over the same period of time (green circles). (b) Under physiological conditions, noxious stimuli activate nociceptive afferent fibres (A_δ and C fibres). Incoming action potentials trigger a release of excitatory transmitter glutamate in the spinal dorsal horn and neuropeptides including substance P (SP) and neurokinin A (NKA). Glutamate and neuropeptides activate spinal dorsal horn neurons, including those that send projection terminals to supraspinal structures. Neurons in the thalamus play key roles in relaying these ascending inputs. Several cortical areas are activated, including the ACC, prefrontal cortex (PFC), insular cortex (IC), primary somatosensory cortex (S1) and secondary somatosensory cortex (S2). Activation of the amygdala (as well as the ACC) also contributes to pain-related fear memory and pain modulation.