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Temporomandibular Joint Pain Measurement by Bite Force and Von Frey Filament Assays in Mice
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Infiltrated Macrophages Aggravate TMJOA Chronic Pain via Piezo2 in IB4+-TG Neurons

Xueke Jia1,2, Xin Liu1,2, Taomin Zhu1,2

  • 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Oral Diseases
|March 7, 2025
PubMed
Abstract

Insights

Infiltrated macrophages worsen temporomandibular joint osteoarthritis (TMJOA) pain by increasing Piezo2 ion channel expression in trigeminal ganglion neurons. Reducing macrophages alleviates TMJOA pain, but this effect is blocked by Piezo2 upregulation.

Area of Science:

  • Neuroscience
  • Immunology
  • Pain Research

Background:

  • Macrophages in ganglia are implicated in chronic pain.
  • Piezo2 ion channels are crucial for pain sensation.

Purpose of the Study:

  • To investigate the interaction between macrophages and Piezo2 in temporomandibular joint osteoarthritis (TMJOA) chronic pain.
  • To understand the role of macrophages in regulating Piezo2 expression in TMJOA pain.

Main Methods:

  • Temporomandibular joint osteoarthritis (TMJOA) induced in rats using monosodium iodoacetate (MIA).
  • Macrophage depletion using clodronate liposomes and Piezo2 overexpression in trigeminal ganglion (TG) neurons via AAV9-Piezo2.
  • Pain thresholds assessed using the Rat Grimace Scale (RGS); molecular analyses included immunofluorescence and in vitro studies.

Main Results:

  • Positive correlation found between macrophage infiltration and Piezo2 upregulation in TG neurons of TMJOA rats.
  • Macrophage depletion reduced Piezo2 levels and pain, while Piezo2 overexpression reversed these effects.
  • Macrophages primarily affect Piezo2 expression in IB4+-TG neurons, with IL-1β and TNF-α cytokines mediating this activation.

Conclusions:

  • Infiltrated macrophages exacerbate MIA-induced TMJOA chronic pain by upregulating Piezo2 expression in IB4+-TG neurons.
  • Targeting macrophage-derived cytokines may offer a therapeutic strategy for TMJOA pain.
Keywords:
Piezo2ion channelsmacrophagesosteoarthritistemporomandibular jointtrigeminal ganglion

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