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Macrophage as a Peripheral Pain Regulator

Risa Domoto1, Fumiko Sekiguchi1, Maho Tsubota1

  • 1Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka 577-8502, Japan.

Cells
|August 27, 2021
PubMed

Insights

Macrophages and neurons engage in critical neuroimmune crosstalk, influencing pathological pain. This interaction involves various macrophage types and mediators, highlighting their role in pain signaling.

Area of Science:

  • Neuroscience
  • Immunology
  • Pain Research

Background:

  • Neuroimmune crosstalk is integral to pathological pain, encompassing inflammatory and neuropathic conditions.
  • Macrophages, including microglia, infiltrating macrophages, and tissue-resident macrophages, play a key role in processing and regulating pain signals.
  • Recent research highlights novel aspects of tissue-resident macrophages, including their origins and involvement in pain modulation.

Purpose of the Study:

  • To elucidate the multifaceted roles of macrophages in neuroimmune interactions within pain pathways.
  • To explore the contribution of different macrophage populations (tissue-resident and infiltrating) to somatic and visceral pain.
  • To understand the bidirectional communication between neurons and macrophages in the context of pain signaling.

Main Methods:

  • Review and synthesis of recent scientific literature on neuroimmune interactions in pain.
  • Analysis of the mediators secreted by various macrophage types and their effects on primary afferents.
  • Examination of neuron-derived mediators and their influence on macrophage activity.

Main Results:

  • Peripheral nerve and intestinal resident macrophages, along with monocyte-derived infiltrating macrophages, secrete key mediators (e.g., TNF-α, IL-1β, IL-6, HMGB1, BMP2) that modulate primary afferent neuron excitability.
  • Neurons release mediators (e.g., neuropeptides, ATP, M-CSF) that regulate macrophage activity and polarization.
  • Macrophages exhibit diverse functions in homeostasis and actively participate in pathological pain by interacting with neurons.

Conclusions:

  • Macrophages are crucial players in neuroimmune crosstalk, significantly impacting somatic and visceral pathological pain.
  • The bidirectional communication between macrophages and neurons, involving a complex array of secreted mediators, is fundamental to pain regulation.
  • Understanding these macrophage-neuron interactions offers potential therapeutic targets for pain management.
Keywords:
dorsal root ganglioninflammatory painmacrophageneuroimmune crosstalkneuropathic painprimary afferentvisceral pain

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