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Relief from neuropathic pain by blocking of the platelet‐activating factor‐pain loop
Author(s) -
Shindou Hideo,
Shiraishi Seiji,
Tokuoka Suzumi M.,
Takahashi Yoshikazu,
Harayama Takeshi,
Abe Takaya,
Bando Kana,
Miyano Kanako,
Kita Yoshihiro,
Uezono Yasuhito,
Shimizu Takao
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601183r
Subject(s) - neuropathic pain , analgesic , platelet activating factor , lysophosphatidic acid , pharmacology , medicine , platelet activating factor receptor , antagonist , receptor antagonist , receptor , anesthesia
Neuropathic pain resulting from peripheral neuronal damage is largely resistant to treatment with currently available analgesic drugs. Recently, ATP, lysophosphatidic acid, and platelet‐activating factor (PAF) have been reported to play important inductive roles in neuropathic pain. In the present study, we found that pain‐like behaviors resulting from partial sciatic nerve ligation (PSL) were largely attenuated by deficiency of lysophosphatidylcholine acyltransferase (LPCAT)2, which is one of the PAF biosynthetic enzymes. By contrast, deficiency of the other PAF biosynthetic enzyme, LPCAT1, did not ameliorate neuropathic pain. With regard to the mechanism of the observed effects, LPCAT2 was detected in wild‐type spinal cord microglia, and the absence of LPCAT2 expression precluded spinal PAF expression in LPCAT2‐knockout mice. Furthermore, ATP‐stimulated PAF biosynthesis in macrophages was decreased by pretreatment with the PAF receptor antagonist ABT‐491, indicating the existence of a positive feedback loop of PAF biosynthesis, which we designated the PAF–pain loop. In conclusion, LPCAT2 is a novel therapeutic target for newly categorized analgesic drugs; in addition, our data call for the reevaluation of the clinical utility of PAF receptor antagonists.—Shindou, H., Shiraishi, S., Tokuoka, S. M., Takahashi Y., Harayama, T., Abe, T., Bando, K., Miyano, K., Kita, Y., Uezono, Y., Shimizu, T. Relief from neuropathic pain by blocking of the platelet‐activating factor–pain loop. FASEB J. 31, 2973–2980 (2017). www.fasebj.org