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Nociceptive signaling of P2X receptors in chronic pain states

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Abstract

P2X3 monomeric receptors (P2X3Rs) and P2X2/3 heteromeric receptors (P2X2/3Rs) in primary sensory neurons and microglial P2X4 monomeric receptors (P2X4Rs) in the spinal dorsal horn (SDH) play important roles in neuropathic pain. In particular, P2X4R in the spinal microglia during peripheral nerve injury (PNI), experimental autoimmune neuritis, and herpes models are useful to explore the potential strategies for developing new drugs to treat neuropathic pain. Recently, novel P2X4 antagonists, NP-1815-PX and NC-2600, were developed, which demonstrated potent and specific inhibition against rodent and human P2X4Rs. The phase I study of NC-2600 has been completed, and no serious side effects were reported. The roles played by purinergic receptors in evoking neuropathic pain provide crucial insights into the pathogenesis of neuropathic pain.

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Funding

This work was supported partly by JSPS KAKENHI Grant Numbers 25117013 and the Core Research for Evolutional Science and Technology (AMED-CREST) program from Japan Agency for Medical Research and Development. I also thank Drs. Makoto Tsuda, Hidetoshi Tozaki-Saitoh, Takahiro Masuda and many students for the experiments. I thank Lisa Giles, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/ac) for suggesting to edit a draft of this manuscript.

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  1. Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kazuhide Inoue

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This article is part of the Topical Collection on A Tribute to Professor Geoff Burnstock.

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Inoue, K. Nociceptive signaling of P2X receptors in chronic pain states. Purinergic Signalling 17, 41–47 (2021). https://doi.org/10.1007/s11302-020-09743-w

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