► Latest insights into synaptic mechanisms of hyperalgesia including the recently discovered opioid-withdrawal LTP. ► Depiction of distinct signalling pathways for the induction and for the maintenance of LTP. ► Emerging role of glial cells for LTP at synapses of nociceptive primary afferents. ► Description of newly discovered reversal of LTP by clinically approved drugs. ► We argue that LTP at synapses of nociceptive nerve fibres is an element of a biological cascade amplifier in a nociceptive daisy chain.
Long-term potentiation of synaptic strength (LTP) in nociceptive pathways shares principle features with hyperalgesia including induction protocols, pharmacological profile, neuronal and glial cell types involved and means for prevention. LTP at synapses of nociceptive nerve fibres constitutes a contemporary cellular model for pain amplification following trauma, inflammation, nerve injury or withdrawal from opioids. It provides a novel target for pain therapy. This review summarizes recent progress which has been made in unravelling the properties and functions of LTP in the nociceptive system and in identifying means for its prevention and reversal.