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X : The nociceptive system enables us to respond in time to external threats that otherwise would produce tissue damage. By monitoring tissue composition the system also contributes to bodily homeostasis. Nociceptors signal mechanical stress, extreme temperatures, cell injury and inflammation. Powerful modulation of nociceptive signals occurs in the spinal dorsal horn, so that their further transmission to the brain can be enhanced or inhibited. A vast array of transmitters and receptors are responsible for complex synaptic interactions in the dorsal horn. Synaptic plasticity alters neuronal excitability for hours to months (years?), contributing to hyperalgesia and chronic pain. Descending monoaminergic connections from the brain stem can inhibit or facilitate the signal transmission from nociceptors. These systems are partly controlled by ascending signals from the dorsal horn, partly by descending connections from amygdala, hypothalamus and the cerebral cortex. The latter are thought to contribute to context-dependent pain modulation. The subjective experience of pain correlates with increased activity in a cortical network including the insula, the cingulate gyrus and some other areas. The activity of the network is also positively correlated with expectation of pain, and negatively correlated with expectation of pain relief--independent of nociceptor stimulation.

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