Pain, nociception and inflammation; insights into the mechanisms and possible therapeutic approaches

Abstract

Pain is a complex phenomenon and the disentangling of the underlying mechanisms, in which peripheral and central inflammation play an important role, leads to new insights and new therapeutic options. Peripheral inflammation is characterised by the release of a great variety of substances and inflammatory mediators, such as prostaglandines, cytokines and growth factors. The nociceptors at the extreme ends of the C-fibers register changes in the local milieu. It is the specific receptors and transducer proteins located on the nociceptor that cause a depolarisation and in that way send an action potential via the C-fibres to the central nervous system. Upon arrival of this action potential, an inflammatory response will also develop in the central nervous system in which microglial cells play a pivotal role. The interaction between the activated microglial cells and the central sensitization process (NMDA receptor) may result in chronification of the pain.