Emerging concepts of pain therapy based on neuronal mechanisms

Current pain treatment is successful in many patients, but nevertheless numerous problems have to be solved because still about 20% of the people in the population suffer from chronic pain. A major aim of pain research is, therefore, to clarify the neuronal mechanisms which are involved in the generation and maintenance of different pain states and to identify the mechanisms which can be targeted for pain treatment. This volume on pain control addresses neuronal pain mechanisms at the peripheral, spinal, and supraspinal level which are thought to significantly contribute to pain and which may be the basis for the development of new treatment principles. This introductory chapter addresses the types of pain which are currently defined based on the etiopathologic considerations, namely physiologic nociceptive pain, pathophysiologic nociceptive pain, and neuropathic pain. It briefly describes the structures and neurons of the nociceptive system, and it addresses molecular mechanisms of nociception which may become targets for pharmaceutical intervention. It will provide a frame for the chapters which address a number of important topics. Such topics are the concept of hyperalgesic priming, the role of voltage-gated sodium channels and nerve growth factor (NGF) in different inflammatory and neuropathic pain states, the hyperalgesic effects of NGF in different tissues, the contribution of proteinase-activated receptors (PARs) to the development of pain in several chronic pain conditions, the role of spinal NO and of glial cell activation in the generation and maintenance of inflammatory and neuropathic pain, the potential role of spinal inhibitory interneurons, the endogenous endocannabinoid system, and the importance of nonneuronal immune mechanisms in opioid signaling in the control of pain, the influence of spinal mechanisms on the expression of peripheral inflammation, the role of the amygdala and their connections to the medial prefrontal cortex in pain states, the experimental methods to test central sensitization of the nociceptive system in humans, and differences and similarities of the neuronal systems of pain and itch. Finally it will be discussed that both the concentration on single key molecules of nociception and the interference with disease-related mediators may provide novel approaches of pain treatment.