Pain is unlike other sensations in that the perceived intensity increases with time in the presence of a constant stimulus, in a process called sensitization or hyperalgesia, while in all other senses adaptation ensures that the perceived intensity decreases with time. Hyperalgesia is not intrinsic to the pain-sensitive ending, but instead depends on the release of a range of pro-inflammatory factors, such as bradykinin, prostaglandins and nerve growth factor (NGF), from surrounding stressed or damaged tissues. These factors interact with cell-surface receptors on the nociceptive nerve terminal, and signal via a variety of pathways to ion channels involved in generating the nerve impulses which produce the sensation of pain. This presentation will review recent advances in our understanding of the variety of cellular pathways involved in hyperalgesia, and of how the activity of the ion channels to which they signal is enhanced.