Pain is unique among sensations in that the perceived intensity increases, or sensitizes, during exposure to a strong stimulus. Efforts to determine how neurons sense pain-producing stimuli of a thermal, mechanical or chemical nature have revealed new signaling mechanisms and brought us closer to understanding the molecular events that facilitate transitions from acute to chronic pain. The thermo-gated transient receptor potential (TRP) channels play a critical role in the development of thermal hyperalgesia induced by a wide range of inflammatory mediators. Temperature sensing can be modulated by phosphorylation of intracellular residues by these protein kinases or by insertion of new channels into the cell membrane. Furthermore, the formation of a signaling complex is a final common element in heat hyperalgesia, on which the effects of multiple proinflammatory mediators converge. The integration of A kinase anchoring protein (AKAP) in inflammatory hyperalgesia may be a promising target for the development of novel analgesics.