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Bioactive Lipid Mediators pp 223–236Cite as

Lipid Mediator LPA-Induced Demyelination and Self-Amplification of LPA Biosynthesis in Chronic Pain Memory Mechanisms

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Abstract

Chronic pain is considered to have a memory process because of its long-lasting nature even after the original cause such as nerve injury is resolved. This type contrasts to the cases with acute pain, nociceptive or inflammatory pain, which vanishes without delay after the cessation of stimulation or inhibition of the original inflammation. Lysophosphatidic acid (LPA) was identified to be a key initiator of neuropathic pain, one of the representative types of chronic pain, via activation of multiple machineries. Recent studies revealed that LPA induces LPA biosynthesis through actions of microglia and interleukin-1β. LPA1 and LPA3 receptor-mediated mechanisms are involved in this self-amplification of LPA production. Neuropathic pain is characterized as unique abnormal pain allodynia, in which gentle touch causes intense pain. The functional switch in allodynia is reasonably explained by demyelination, whose underlying mechanisms are also explained as downstream machineries of LPA and its LPA1 receptor signaling. The conversion of tactile to intense pain caused by demyelination may be involved in the long-lasting feed-forward machineries in neuropathic pain. Recent reports describe the importance of endocannabinoids and new arachidonic acid metabolites in the regulation of chronic pain. This chapter also describes the possible relationships of LPA to these additional regulatory mechanisms.

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Abbreviations

ATX:

autotaxin

BDNF:

brain-derived neurotrophic factor

CFA:

complete Freund’s adjuvant

cPLA2 :

cytosolic phospholipase A2

DRG:

dorsal root ganglia

ERK:

extracellular signal-regulated kinase

GABA:

gamma-aminobutyric acid

IL-1β:

interleukin-1β

iPLA2 :

calcium-independent PLA2

JNK:

c-Jun N-terminal kinase

LPA:

lysophosphatidic acid

LPC:

lysophosphatidyl choline

MAG:

myelin-associated glycoprotein

MAPK:

mitogen-activated protein kinase

NSAID:

nonsteroidal antiinflammatory drug

ROCK:

Rho-kinase

sEH:

soluble epoxide hydrolase

SP:

substance, P

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan

    Hiroshi Ueda & Hitoshi Uchida

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  1. Hiroshi Ueda
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  2. Hitoshi Uchida
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Correspondence to Hiroshi Ueda .

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  1. Department of Biochemistry, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Takehiko Yokomizo

  2. Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Makoto Murakami

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Ueda, H., Uchida, H. (2015). Lipid Mediator LPA-Induced Demyelination and Self-Amplification of LPA Biosynthesis in Chronic Pain Memory Mechanisms. In: Yokomizo, T., Murakami, M. (eds) Bioactive Lipid Mediators. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55669-5_16

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