Periodate oxidized ATP (oATP) reduces hyperalgesia in mice: involvement of P2X7 receptors and implications for

A Fulgenzi1, P Ticozzi, C A Gabel

  • 1Institute of General Pathology, University of Milan, Milan Italy.

Insights

Orophosphaote (oATP), an inhibitor of P2X7 receptors, reduces pain in various models, including neuropathic and visceral pain. P2X7 receptor knockout mice show resistance to pain, highlighting P2X7 receptors

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Inflammatory mediators significantly contribute to inflammatory, neuropathic, and visceral pain.
  • Orophosphaote (oATP), a P2X7 receptor inhibitor, previously demonstrated antihyperalgesic effects in experimental inflammation.

Purpose of the Study:

  • To investigate the antihyperalgesic effect of oATP in mouse models of neuropathic and visceral pain.
  • To evaluate the role of P2X7 receptors in arthritic, neuropathic, and visceral pain.

Main Methods:

  • Administration of oATP in mouse models of arthritic, neuropathic, and visceral pain.
  • Assessment of pain responses in P2X7 receptor knockout (KO) mice.
  • Evaluation of ATP-induced hyperalgesia in wild-type and KO mice.

Main Results:

  • oATP exhibited antihypergesic effects in neuropathic and visceral pain models, as well as an arthritic pain model.
  • P2X7 receptor KO mice were resistant to hyperalgesic stimuli across all tested pain models.
  • Local pre-treatment with oATP prevented ATP-dependent hyperalgesia in wild-type mice.

Conclusions:

  • P2X7 receptors are critically involved in pain transmission across inflammatory, neuropathic, and visceral pain states.
  • Targeting P2X7 receptors with inhibitors like oATP represents a potential therapeutic strategy for diverse pain conditions.