Acute noxious stimuli activate a specialized neuronal detection system that generates sensations of pain and, generally, adaptive behavioral responses. More persistent noxious stimuli notably those associated with some chronic injuries and disease states not only activate the pain-signaling system but also dramatically alter its properties so that weak stimuli produce pain. These hyperalgesic states arise from at least two distinct broad classes of mechanisms. These are peripheral and central sensitization associated with increased responsiveness of peripheral nociceptor terminals and dorsal horn neurons, respectively. Here we review the key features of these sensitized states and discuss the role of one neurotrophic factor, nerve growth factor, as a peripheral mediator of sensitization and of another factor, brain-derived neurotrophic factor, as a mediator of central sensitization. We use as a specific example the pain induced by acid stimuli. We review the neurobiology of such pain states, and discuss how acid stimuli both initiate sensitization and how the neuronal processing of acid stimuli is subject to sensitization.