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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
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.
Abstract:
Some inflammatory mediators play an important role not only in the pathogenesis of the inflammatory pain, but also in that of neuropathic and visceral pain. We previously showed the antihyperalgesic effect of oATP, the inhibitor of the P2X7 receptors for the pro-nociceptive ATP, in experimental inflammation. Here we show the antihyperalgesic effect of oATP in mouse models of neuropathic and visceral pain, other than in a model of arthritic pain mimicking rheumatoid arthritis in humans. We also show that mice lacking P2X7 receptors (KO) are resistant to hyperalgesic thermal stimuli following the induction of arthritic, neuropathic and visceral pain. Local (injection into the right hind paw) pre-treatment with oATP is able to prevent the successive induction of ATP-dependent hyperalgesia in wild type mice. In addition, KO mice are not insensitive to intraplantar treatment with ATP. Our data suggest that, even if oATP is able to inhibit purinoceptors different from P2X7, the latter are the more important involved in pain transmission.
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.
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