Pain and the Triple Network Model

Abstract

Acute pain is a physiological response that causes an unpleasant sensory and emotional experience in the presence of actual or potential tissue injury. Anatomically and symptomatically, chronic pathological pain can be divided into three distinct but interconnected pathways, a lateral "painfulness" pathway, a medial "suffering" pathway and a descending pain inhibitory circuit. Pain (fullness) can exist without suffering and suffering can exist without pain (fullness). The triple network model is offering a generic unifying framework that may be used to understand a variety of neuropsychiatric illnesses. It claims that brain disorders are caused by aberrant interactions within and between three cardinal brain networks: the self-representational default mode network, the behavioral relevance encoding salience network and the goal oriented central executive network. A painful stimulus usually leads to a negative cognitive, emotional, and autonomic response, phenomenologically expressed as pain related suffering, processed by the medial pathway. This anatomically overlaps with the salience network, which encodes behavioral relevance of the painful stimuli and the central sympathetic control network. When pain lasts longer than the healing time and becomes chronic, the pain- associated somatosensory cortex activity may become functionally connected to the self-representational default mode network, i.e., it becomes an intrinsic part of the self-percept. This is most likely an evolutionary adaptation to save energy, by separating pain from sympathetic energy-consuming action. By interacting with the frontoparietal central executive network, this can eventually lead to functional impairment. In conclusion, the three well-known pain pathways can be combined into the triple network model explaining the whole range of pain related co-morbidities. This paves the path for the creation of new customized and personalized treatment methods.

Keywords: acute; anterior cingulate cortex; autonomic; chronic; cognitive; emotional; pain; triple network.

Figure 1

Overview of the history of pain research.

Figure 2

(A) The anatomical pathways associated with 3 different aspects of pain (painfulness, suffering and presence). (B) Neurosynth meta-analyses of functional imaging studies evaluating the different components of the pain signature in the brain. Meta-analysis of pain (n = 516 studies, red and blue), meta-analysis of suffering (n = 124, green) and meta-analysis of inhibition (n = 601, purple). Modified from reference De Ridder et al. (29).

Figure 3

Neurosynth meta-analysis of chronic pain. The pre to subgenual anterior cingulate component is absent, suggesting that chronic pain is related to lost inhibition. Modified from reference De Ridder et al. (29).

Figure 4

Triple Network model. The salience and central executive networks are correlated, and both are anti-correlated to the default mode network.

Figure 5

A chronic painful stimulus leads to a cognitive, emotional, and autonomic response, which phenomenologically expresses as catastrophizing, attention paid to the pain, unpleasantness, fear, anger or frustration with pain and arousal/distress. These cognitive, emotional, and autonomic symptoms are all phenomenological expressions of altered activity in the medial pathway.

Figure 6

Neurosynth meta-analysis of the central autonomic network (n = 117 studies).

Figure 7

The presence of a painful stimulus in the lateral somatosensory pathway, can lead to a cognitive, emotional, and autonomic response, encoded by the medial salience pathway expressed by suffering. When the pain and suffering become chronic, they become embodied, i.e., part of the self, mediated via connectivity of the somatosensory cortex to the default mode network. The embodied pain and suffering can subsequently lead to physical and cognitive disability, possibly mediated via dysfunctional connectivity with the motor and the central executive network, respectively.