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Peripheral 5-HT3 mediates mirror-image pain by a cross-talk with acid-sensing ion channel 3

Yeu-Shiuan Su1, Hao-Ruei Mei1, Chun-Hung Wang1

  • 1Department of Life Sciences, National Central University, Zhongli District, Taoyuan city, Taiwan.

Neuropharmacology
|December 3, 2017
PubMed

Insights

Mirror-image pain, a condition causing pain sensitivity in uninjured areas, is triggered by the interaction of serotonin 3 (5-HT3) and acid-sensing ion channel 3 (ASIC3) receptors, leading to glial activation.

Area of Science:

  • Neuroscience
  • Pain Research
  • Molecular Biology

Background:

  • Mirror-image pain (MIP) involves heightened pain sensitivity in healthy body regions, often accompanying conditions like complex regional pain syndrome.
  • Peripheral inflammation is suspected to activate glia, leading to MIP, but the specific receptors involved remain unidentified.

Purpose of the Study:

  • To investigate the molecular mechanisms and receptors mediating inflammatory signals that trigger glial activation and mirror-image pain.
  • To identify the specific receptors responsible for inflammatory signal transduction leading to glial activation and MIP.

Main Methods:

  • Induction of hyperalgesia in mice using intraplantar injections of 5-hydroxytryptamine (5-HT) or acidic buffer, individually and in combination.
  • Assessment of MIP by blocking serotonin 3 (5-HT3) and acid-sensing ion channel 3 (ASIC3) receptors, and using agonists/antagonists for these channels.
  • Examination of 5-HT3 and ASIC3 co-localization and functional interaction in dorsal root ganglion (DRG) neurons using calcium imaging.

Main Results:

  • Co-injection of 5-HT and acid induced bilateral hyperalgesia (MIP), while individual injections caused only unilateral effects.
  • Blocking 5-HT3 or ASIC3 receptors abolished satellite glial activation and inhibited MIP.
  • Both 5-HT3 and ASIC3 agonists induced MIP, and their effects could be reversed by antagonists of the respective channels or blockers of the other channel.
  • 5-HT3 and ASIC3 were found to co-localize in DRG neurons, with functional cross-talk observed in calcium signaling.

Conclusions:

  • A cross-talk between 5-HT3 and ASIC3 receptors mediates satellite glial activation, which is a key mechanism triggering mirror-image pain.
  • Targeting the interaction between 5-HT3 and ASIC3 may offer a novel therapeutic strategy for managing mirror-image pain.
Keywords:
5-HT(3)AcidAcid-sensing ion channel 3Mirror image painSerotonin

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