The link between chronic pain and Alzheimer's disease

Song Cao, Daniel W. Fisher, Tain Yu, Hongxin Dong*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

78 Scopus citations


Chronic pain often occurs in the elderly, particularly in the patients with neurodegenerative disorders such as Alzheimer's disease (AD). Although studies indicate that chronic pain correlates with cognitive decline, it is unclear whether chronic pain accelerates AD pathogenesis. In this review, we provide evidence that supports a link between chronic pain and AD and discuss potential mechanisms underlying this connection based on currently available literature from human and animal studies. Specifically, we describe two intertwined processes, locus coeruleus noradrenergic system dysfunction and neuroinflammation resulting from microglial pro-inflammatory activation in brain areas mediating the affective component of pain and cognition that have been found to influence both chronic pain and AD. These represent a pathological overlap that likely leads chronic pain to accelerate AD pathogenesis. Further, we discuss potential therapeutic interventions targeting noradrenergic dysfunction and microglial activation that may improve patient outcomes for those with chronic pain and AD.

Original languageEnglish (US)
Article number204
JournalJournal of neuroinflammation
Issue number1
StatePublished - Nov 6 2019


  • Alzheimer's disease
  • Chronic pain
  • Locus coeruleus
  • Microglia
  • Noradrenergic system
  • Norepinephrine
  • Prefrontal cortex

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Immunology


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