Bottom-up Processing of Pain

Today we know that there is not a pain center in which the final pain experience emerges, but rather there is a distributed system that is made up of an intricate network of cortical and subcortical areas, each with some specific functions. This network is often referred to as the “pain matrix.”

The organization of the nociceptive pathways and areas from the spinal cord to the higher centers (bottom-up processing) is quite complex. Part of the spinothalamic tract, the lateral thalamus, and its cortical projections to the first somatosensory area (SI) is usually considered to be crucial for pain perception.

The neurons in these regions are somatotopically ordered and have small contralateral receptive fields. This system, which is shown in bold in Fig. 4.1, with its precise somatotopic organization, encodes the sensory-discriminative aspects of pain sensation and is called “lateral system.”

Fig. 4.1 Schematic organization of the lateral (bold) and medial pain systems. Reproduced from Physiological Reviews, 93 (3), Placebo and the New Physiology of the Doctor-Patient Relationship, Fabrizio Benedetti, pp.1207–1246, figure 4, DOI: 10.1152/physrev.00043.2012 Copyright 2013, The American Physiological Society.

Parallel and complementary to this lateral pain system, a “medial system” exists, whose functions deal with the affective-emotional component of pain, i.e., those aspects regarding its unpleasantness, its negative hedonic quality, and the negative emotions associated with it. Without this emotional aspect, which in one word can be called “suffering,” the pain experience is incomplete and can hardly be defined as such.

In Fig. 4.1 some of the main regions involved in the medial pain system are shown, e.g., the medial thalamus, the insula and the parietal operculum, the prefrontal and orbitofrontal, as well as the anterior and posterior cingulate cortices. Many of these areas are strongly connected with one another and with many other regions of the limbic system.

In contrast to the lateral pain system, here the somatotopic organization is generally lacking, suggesting a role in nonspecific arousal rather than its precise spatial and temporal localization. Therefore, whereas the lateral system is responsible for the discriminative properties of pain perception, that is, how intense pain is, how long it lasts, and where it is localized, the medial pain system is responsible for the effective component, that is, how long pain can be tolerated and how much suffering it produces.

This sensory dissociation of pain is also shown by people with brain lesions that involve the medial system (mainly the limbic system). These patients can recognize pain as such and can discriminate its intensity, duration, and localization. However, they can tolerate it for longer times, reporting that the pain does not produce much suffering. The lateral and medial pain systems are affected differently in dementia of the Alzheimer’s type (The Lateral and Medial Pain Systems in Alzheimer’s Disease).


Benedetti, Fabrizio. Placebo Effects (p. 111). OUP Oxford.