Enhancement of purinergic signalling by excessive endogenous ATP in resiniferatoxin (RTX) neuropathy |
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Authors: | Chih-Lung Lin Yaw-Syan Fu Tin-Hsin Hsiao Yu-Lin Hsieh |
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Institution: | 1. Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan 2. Faculty of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan 3. Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan 4. Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan
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Abstract: | ATP is a ligand of P2X family purinoceptors, and exogenous ATP administration evokes pain behaviors. To date, there is a lack of systematic studies to address relationships between endogenous ATP and neuropathic pain. In this report, we took advantage of a mouse model of resiniferatoxin (RTX)-induced neuropathic pain to address the role of endogenous ATP in neuropathic pain. After RTX administration, endogenous ATP markedly increased in dorsal root ganglia (DRGs) (p?<?0.01) and skin tissues (p?<?0.001). The excessive endogenous ATP was removed by apyrase, an ATP hydrolyzing enzyme, administration via either a lumbar puncture route (p?<?0.001) or an intraplantar injection (p?<?0.001), which led to the normalization of neuropathic pain. In addition, intraplantar treatment with apyrase caused mechanical analgesia. Linear analyses showed that the densities of P2X3(+) neurons (r?=??0.72, p?<?0.0001) and P2X3(+) dermal nerves (r?=??0.72, p?<?0.0001) were inversely correlated with mechanical thresholds. Moreover, the contents of endogenous ATP in skin tissues were linearly correlated with P2X3(+) dermal nerves (r?=?0.80, p?<?0.0001) and mechanical thresholds (r?=??0.80, p?<?0.0001). In summary, this study demonstrated that enhanced purinergic signalling due to an increase in endogenous ATP after RTX-induced nerve injury contributed to the development of neuropathic pain. The data in this report provide a new therapeutic strategy for pain control by targeting the endogenous ligand of purinergic signalling. |
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