Figure 1

Neuropathic pain is manifested through alterations at the peripheral, spinal, and cortical levels. At the periphery, neuropathic pain is associated with changes in the excitability of nociceptors. At the spinal cord level, long-term potentiation (LTP) of sensory excitatory synaptic transmission take place at least at similar time scales. The upregulation of postsynaptic AMPA receptors including possible recruitment of silent synapses contribute to spinal LTP. Similar to LTP reported in other central synapses, different protein kinases and possible new protein synthesis are also required. Within the cortex, neuropathic pain is associated with the induction of LTP including late-phase LTP (L-LTP) at cortical synapses. Both presynaptic and postsynaptic alterations have been observed that result in ongoing potentiated excitatory activity. Dis-inhibition of local inhibitory modulation have been also found within the spinal dorsal horn and cortical areas. Descending faciltiatory modulation from cortical and sub-cortical areas are also thought to contribute to enhanced sensory transmission in the spinal cord dorsal horn.