Peripheral and central viewpoints of chronic pain, and translational implications

Abstract

This overview covers advances in mechanisms of chronic pain and their consequent clinical opportunities. Our research field is fractured into two separate camps: "peripheralists" and "centralists". While the strong position of the first group is the contention that mechanisms of chronic pain can be understood within the limits of afferent inputs and spinal cord circuitry, the second group insists that the rest of the brain plays a critical role. Here we attempt to conjoin these positions, across clinical pain conditions and animal studies, and demonstrate that the effort can lead to novel translational concepts.

Keywords: Brain imaging; Chronic pain; Limbic system; Sensory testing; Spinal cord.

Figure 1:. Distinct stages for chronic pain.

Predispositions are pre-existing factors that place some individuals at risk for developing chronic pain following an injury. Duration of the transition state may be dependent on type of injury as well as also based on predisposing factors. The interaction between injury and predispositions generate the transition state which may, or not, lead to a new brain state of maintenance of chronic pain. The “peripheralist” viewpoint posits that all four stages are determined by nociceptive properties, controlled primarily by peripheral afferents and their interaction with spinal cord circuitry. The “centralists” advance the notion that predispositions are mainly determined by limbic brain properties, and that the interaction between nociceptive circuitry and predispositions creates the transition state, where brain learning and memory circuitry interact with the cortex to give rise to the neocortical state of chronic pain.