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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

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Multiple P2Y subtypes in spinal microglia are involved in neuropathic pain after peripheral nerve injury

Kimiko Kobayashi1, Hiroki Yamanaka, Fujio Yanamoto

  • 1Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.

Glia
|June 28, 2012
PubMed

Insights

Neuropathic pain involves microglial purinergic receptors. This study shows P2Y6, P2Y12, P2Y13, and P2Y14 receptors are upregulated after nerve injury and contribute to pain development.

Area of Science:

  • Neuroscience
  • Pain Research
  • Molecular Biology

Background:

  • Neuropathic pain pathogenesis involves microglial purinergic signaling.
  • P2Y12 receptors are known to be upregulated post-nerve injury, influencing pain behavior.
  • The role of other P2Y receptors in neuropathic pain remains less understood.

Purpose of the Study:

  • To investigate the expression of P2Y6, P2Y13, and P2Y14 receptors in the spinal cord following peripheral nerve injury.
  • To determine the involvement of these P2Y receptors in the development of neuropathic pain.
  • To explore the relationship between p38 MAPK signaling and P2Y receptor expression.

Main Methods:

  • Spared nerve injury model in rodents.
  • Quantitative real-time PCR to assess mRNA expression of P2Y receptors in spinal microglia.
  • Intrathecal administration of p38 MAPK inhibitor (SB203580).
  • Intrathecal administration of specific antagonists/antisense for P2Y6, P2Y13, and P2Y14 receptors.
  • Assessment of mechanical pain hypersensitivity.

Main Results:

  • Spared nerve injury significantly increased mRNA expression of P2Y6, P2Y12, P2Y13, and P2Y14 receptors in spinal microglia for at least two weeks.
  • p38 MAPK inhibition suppressed P2Y6, P2Y13, and P2Y14 mRNA expression but not P2Y12.
  • Pharmacological blockade of P2Y6, P2Y13, or P2Y14 receptors attenuated mechanical pain hypersensitivity.
  • A combination of antagonists for P2Y6, P2Y12, and P2Y13 receptors demonstrated a more prolonged suppression of pain behavior.

Conclusions:

  • ATP and other nucleotides activate microglia, leading to the upregulation of P2Y6, P2Y12, P2Y13, and P2Y14 receptors after nerve injury.
  • These upregulated P2Y receptors play a crucial role in the pathogenesis of neuropathic pain.
  • Targeting these purinergic receptors represents a potential therapeutic strategy for neuropathic pain management.

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