[Mechanisms in the development of pain. Key issue in the periphery]

The interaction between neurons, tissue cells and inflammatory cells is of major importance for the development of pain in the periphery. In this interaction a variety of inhibitory and activating circuits has been identified in recent years. In addition to the receptors for classical inflammatory mediators on the sensory terminals like bradykinin, axonal ion channels have been identified as major modulators of pain and sensitization apart from their traditional role in conduction of action potentials. Sensitization of spinal nociceptive processing is crucial for the expansion of pain beyond the initially injured site and contributes to chronic pain. Learning processes and extinction of aversive memory are of major importance for the development, but also the therapy of chronic pain states.