Neuroanatomy and Pathophysiology of Pain Perception Abstract. Nociception, the possibility of our sensory nervous system to detect painful and therefore potentially harmful stimuli, is crucial for survival. In essence it serves as a "detect and protect" mechanism. For this reason, many features of this complex network, for example the nociceptors, are evolutionary highly preserved. To guarantee an adequate and fast response to prevent tissue damage, the information has to be processed in a fast and stable manner. To this account, the network is designed to be able to potentiate the information at any level. However, sometimes triggered by pathophysiological factors like inflammation, this functional and structural plasticity can become maladaptive, leading to chronification of pain and in this way become a disease itself. Nociception starts in the periphery by activation of a nociceptor which is a highly specialized neuron of the somatosensory nervous system. Some of them are thinly myelinated Aδ fibers, others unmyelinated C fibers. The free nerve endings in the skin or other tissues are equipped with different receptors and ion channels to translate noxious stimuli (like temperature or pressure) into electrochemical signals. These are transmitted to the dorsal horn of the spinal cord, where the second neuron is activated via excitatory amino acids (like glutamate) and other substances, a process which is modulated by inhibitory interneurons. This second neuron projects to cerebral locations, mostly to the thalamus but also to hypothalamus and amygdala, where the usually fast emotional and vegetative reaction is generated. The third order neuron then terminates in the somatosensory cortex and is embedded in a complex network, the so called "pain matrix". Areas involved are for example the prefrontal cortex, where decision making happens, and the limbic structures, where pain memory and learning processes take place. Descending projections from the locus coeruleus, raphe nuclei and the rostroventral medulla oblongata to the spinal cord can either facilitate or inhibit the nociceptive information. Sensitization leading to enhanced activation of the nociceptive pathways can take place at any level, which can become a "circulus vitiosus", finally underlying a chronic pain disorder.
Zusammenfassung. Die Wahrnehmung von Schmerz entspricht der wahrscheinlich komplexesten sensorischen Funktion unseres Nervensystems. Im Kern entspricht die Nozizeption einer evolutionsbiologisch hochrelevanten Warnfunktion, die den Körper vor potentiell schädlichen Reizen schützen soll. Um dies zu gewährleisten, sind auf allen Stufen des Prozesses – sowohl auf molekularer, als auch auf struktureller Ebene und sowohl in der Peripherie als auch im zentralen Nervensystem – rasche und teilweise ausgeprägte Veränderungen möglich und notwendig, um die Anpassung an unterschiedliche Situationen zu ermöglichen. Diese strukturelle und funktionelle Plastizität soll die Information des potentiell schädlichen Einflusses innerhalb kürzester Zeit potenzieren, damit rasch und zielgerichtet reagiert und der Schaden möglichst gering gehalten werden kann. In manchen Fällen führt diese sogenannte periphere und zentrale Sensibilisierung aber zur Ausbildung chronischer Schmerzen und wird damit schliesslich zur eigenständigen Erkrankung. Die neuroanatomischen und (patho-)physiologischen Grundlagen sowie das Ausmass dieser biologischen «Gratwanderung» wie auch einige medizinische und therapeutische Implikationen sollen im Folgenden illustriert werden.