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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- 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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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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DOI: https://doi.org/10.1007/978-4-431-55669-5_16
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