All vertebrate animals possess a sensory system that allows them to detect potentially tissue-damaging (or noxious) stimuli. The proper functioning of this system is essential to protect their bodies from tissue damage. Nerve impulses generated by noxious stimuli are conducted by C and A-delta (nociceptive) primary afferent fibers to the superficial spinal dorsal horn. Spinal neurons receive and process these signals, and in certain conditions transmit them to higher brain centers where nociceptive impulses generate pain. The seminar is going to focus on the first site of synaptic processing of pain-related signals, and intends to give an overview about the molecular anatomy of synaptic contacts between nociceptive primary afferents and spinal sensory neurons. It will be shown that the molecular architecture of these synapses is highly complex that gives various possibilities for pre- and postsynaptic modulation. It will also be emphasized that in addition to being highly complex, the molecular organization of these synaptic contacts shows a high degree of activity evoked plasticity; e.g. enhanced activities of nociceptive primary afferents in certain pathologic conditions like chronic inflammation or nerve injury induce various changes in the molecular organization of these synapses that contribute to the development of central sensitization and chronic pain syndromes.