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Review
, 16 (1), 204

The Link Between Chronic Pain and Alzheimer's Disease

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Review

The Link Between Chronic Pain and Alzheimer's Disease

Song Cao et al. J Neuroinflammation.

Abstract

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.

Keywords: Alzheimer’s disease; Chronic pain; Locus coeruleus; Microglia; Noradrenergic system; Norepinephrine; Prefrontal cortex.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Illustration depicting a possible mechanism of chronic pain induced Alzheimer’s disease pathogenesis through locus coeruleus (LC)-noradrenaline (NE) system dysfunction and microglial neuroinflammation. Chronic pain induces pathological activation of LC-NE system and result in an increase of NE release in brain areas such as the prefrontal cortex and hippocampus, which could be one of the mechanisms of chronic pain-induced microglial pro-inflammatory activation. Pro-inflammatory activation may exacerbate AD pathogenesis via decreased Aβ phagocytosis, increased tau seeding, loss of synaptic function, and cytokine-induced neuron death in these brain regions

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