All higher organisms 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. However, under pathological conditions after severe tissue injury and in inflammatory or neuropathic diseases, this system can become sensitized, and pain can then turn into a disease. Such exaggerated pain sensation (or hyperalgesia) can arise at different levels of integration. It can originate from an increased responsiveness of primary nociceptors, specialized nerve cells, which sense noxious stimuli, or from changes in the central processing of nociceptive input. Like other sensory input, nociceptive signals are relayed in the central nervous system by neurons, which communicate with each other mainly through chemical synapses. Changes in the excitability of these neurons or in the strength of their synaptic coupling provide the cellular basis for many forms of pathological pain. This review focuses on the synaptic processing of pain-related signals in the spinal cord dorsal horn, the first site of synaptic integration in the pain pathway. Particular emphasis is paid to synaptic processes underlying the generation of pathological pain evoked by inflammation or neuropathic diseases.