Pain Pathways and Nervous System Plasticity: Learning and Memory in Pain

Pain Med. 2019 Dec 1;20(12):2421-2437. doi: 10.1093/pm/pnz017.


Objective This article reviews the structural and functional changes in pain chronification and explores the association between memory and the development of chronic pain. Methods PubMed was searched using the terms "chronic pain," "central sensitization," "learning," "memory," "long-term potentiation," "long-term depression," and "pain memory." Relevant findings were synthesized into a narrative of the processes affecting pain chronification. Results Pain pathways represent a complex sensory system with cognitive, emotional, and behavioral influences. Anatomically, the hippocampus, amygdala, and anterior cortex-central to the encoding and consolidation of memory-are also implicated in experiential aspects of pain. Common neurotransmitters and similar mechanisms of neural plasticity (eg, central sensitization, long-term potentiation) suggest a mechanistic overlap between chronic pain and memory. These anatomic and mechanistic correlates indicate that chronic pain and memory intimately interact on several levels. Longitudinal imaging studies suggest that spatiotemporal reorganization of brain activity accompanies the transition to chronic pain, during which the representation of pain gradually shifts from sensory to emotional and limbic structures. Conclusions The chronification of pain can be conceptualized as activity-induced plasticity of the limbic-cortical circuitry resulting in reorganization of the neocortex. The state of the limbic-cortical network determines whether nociceptive signals are transient or chronic by extinguishing pathways or amplifying signals that intensify the emotional component of nociceptive inputs. Thus, chronic pain can be seen as the persistence of the memory of pain and/or the inability to extinguish painful memories. Ideally, pharmacologic, physical, and/or psychological approaches should reverse the reorganization accompanying chronic pain.

Keywords: Chronic Pain; Learning; Limbic; Memory; Pain Chronification; Pain Neurophysiology; Plasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain / physiopathology*
  • Central Nervous System Sensitization / physiology
  • Chronic Pain / physiopathology*
  • Humans
  • Learning / physiology
  • Long-Term Potentiation / physiology
  • Long-Term Synaptic Depression / physiology
  • Memory / physiology*
  • Memory Consolidation / physiology
  • Neural Pathways / physiopathology
  • Neuronal Plasticity / physiology*
  • Nociception
  • Pain / physiopathology
  • Pain Perception