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Zongxiang Tang
Corresponding Author
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Background Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. ATP is an important molecule closely related to many important physiological and pathologic functions. ATP-gated cation channel P2X receptors are widely distributed in various tissues of body, including nervous system and immune system. As an important member of P2X receptors, P2X7 is not only involved in pain, epilepsy, Parkinson’s diseases, but also in the formation of blood, respiratory and digestive diseases. In this study, we investigated the role of P2X receptors in mast cells for peripheral pain and the analgesic mechanism of salicylic acid and aspirin.
Methods P2X receptors were examined and identified in mouse peritoneal mast cells by RT-PCR, intracellular calcium measurement and electrophysiology. The inflammatory mediators released from the activated mast cell were examined by real-time PCR and ELISA. Paw swelling, mechanical stimulation threshold and histopathological changes were tested to evaluate the peripheral pain in mice.
Results The results showed that P2X1, P2X4, P2X7 receptors were expressed in mouse peritoneal mast cells. Mast cell was activated in a concentration-dependent manner by extracellular ATP, and the activation could be blocked by specific ion channel antagonists. In addition, high concentrations of ATP also induced mast cells to release inflammatory mediators such as histamine, IL-1β and CCL3 through P2X7 receptor. Furthermore, peripheral pain of the extracellular high concentration ATP to induce could be alleviated by P2X7 blockers or mast cell defects. We also found that salicylic acid and its derivation aspirin could inhibit high concentration ATP-induced inward current, release of inflammatory factors in mast cells, as well as the peripheral pain caused by high concentration ATP.
Conclusions Together with these, we concluded that extracellular ATP with high concentration could not only activate neurons directly, but also activate P2X7 receptor on mast cells, and induce peripheral pain via neuro-immune crosstalk. Additionally, salicylic and aspirin could inhibit the activity of P2X7, therefore, P2X7 receptor may be one of the potential targets for salicylic acid and aspirin analgesia.
Keywords
ATP, mast cell, P2X7, salicylic acid and aspirin, analgesia
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Zongxiang Tang
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
The most recent version of this article is available here.
No community comments so far
Version 1
Posted 20 May, 2020
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Background Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. ATP is an important molecule closely related to many important physiological and pathologic functions. ATP-gated cation channel P2X receptors are widely distributed in various tissues of body, including nervous system and immune system. As an important member of P2X receptors, P2X7 is not only involved in pain, epilepsy, Parkinson’s diseases, but also in the formation of blood, respiratory and digestive diseases. In this study, we investigated the role of P2X receptors in mast cells for peripheral pain and the analgesic mechanism of salicylic acid and aspirin.
Methods P2X receptors were examined and identified in mouse peritoneal mast cells by RT-PCR, intracellular calcium measurement and electrophysiology. The inflammatory mediators released from the activated mast cell were examined by real-time PCR and ELISA. Paw swelling, mechanical stimulation threshold and histopathological changes were tested to evaluate the peripheral pain in mice.
Results The results showed that P2X1, P2X4, P2X7 receptors were expressed in mouse peritoneal mast cells. Mast cell was activated in a concentration-dependent manner by extracellular ATP, and the activation could be blocked by specific ion channel antagonists. In addition, high concentrations of ATP also induced mast cells to release inflammatory mediators such as histamine, IL-1β and CCL3 through P2X7 receptor. Furthermore, peripheral pain of the extracellular high concentration ATP to induce could be alleviated by P2X7 blockers or mast cell defects. We also found that salicylic acid and its derivation aspirin could inhibit high concentration ATP-induced inward current, release of inflammatory factors in mast cells, as well as the peripheral pain caused by high concentration ATP.
Conclusions Together with these, we concluded that extracellular ATP with high concentration could not only activate neurons directly, but also activate P2X7 receptor on mast cells, and induce peripheral pain via neuro-immune crosstalk. Additionally, salicylic and aspirin could inhibit the activity of P2X7, therefore, P2X7 receptor may be one of the potential targets for salicylic acid and aspirin analgesia.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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