Table 1C.
Other recently described lipids in inflammation and pain.
| Animals/tissue/cell type | Effect | Signaling | Experiment | Experimental details | Target | Refs. |
|---|---|---|---|---|---|---|
| NPD1 (precursor: DHA) | ||||||
| C57BL/6 mice, GPR37-KO mice and Cx3cr1-GFP mice, spinal cord, brain and skin tissue, DRGs, peripheral macrophages, CD1 mice | Antiinflammatory, antinociceptive | Reduction of IL-1β, CCL2 expression, phosphorylation of p38 and ERK, Increase of phagocytosis, expression of IL-10 and TGF-β | In vivo, in vitro | zymosan inflammatory pain model, intraplanar drug injection, in situ hybridization, LacZ staining, IHC, ELISA for IL-1β, TGF-β and IL-10, qPCR, Western Blot analysis, transfection, dot blot assay for lipid-binding protein, Ca-imaging, flow cytometry, phagocytosis assay by epifluorescence microscopy, licking or flinching time measurement, mechanical hypersensitivity via von Frey test, Randall-Selitto, behavioral studies, rotarod test, CCI model, with local peri-surgical pre-treatment of NPD1/PD1, autotomy/axotomy and chamber preference measurements with clonidine, long-term potentiation (LTP) measurements, mechanical allodynia studies, sEPSCs measurements | GPR37 | (Xu et al., 2013b; Bang et al., 2018) |
| S1P | ||||||
| Sprague-Dawley rats, Slprl KO and KD mice, human multiple myeloma cells | Proinflammatory | LPA receptor expression, TNFα and IL-1β release, decrease anti-inflammatory cytokines, p38 signaling, LPC activation | In vivo | intrathecal catheters or osmotic minipump for administration of compounds like fingolimod, D24 or D25, bortezomib injection intra peritoneal, S1pr1 silencing with 27mer dicer-substrate silencer RNA (DsiRNA), mechanical allodynia and hyperalgesia tests via von Frey and the Randall and Sellitto paw pressure test, mass spectrometry, Western Blot analysis, S1PR1 knockdown PCR, immunofluorescence, cytokine assay via multiplex cytokine kit, in vitro whole-cell recordings, tumor cell-killing assay via MTT assay | (Blaho and Hla, 2011; Stockstill et al., 2018) | |
| LPC (precursor: phospholipids) | ||||||
| CHO cells expressing mouse TRPM8, DRG cultures, Wistar rats, WT and TRPA1-KO mice, HEK-293 cells | Pronociceptive | Cold sensitivity | In vivo, in vitro | Ca-imaging, electrophysiology, intracellular calcium assay, subcutaneous injection in paw of icilin, menthol, LPC, BEL, saline, α,β-methylene ATP, Allyl isothiocyanate (AITC), cinnamaldehyde, cold plate and acetone evaporation measurement, heat sensitivity by hot-plate measurements, mechanical sensitivity transfection, iPLA2 activity assay, electrophysiology, fluorescence measurements of cytosolic calcium concentrations | TPM8, iPLA2 | (Vanden Abeele et al., 2006; Andersson et al., 2007; Gentry et al., 2010; Dennis and Norris, 2015) |
| LPA (precursor: lysophospholipids) | ||||||
| Neurons | Pronociceptive at early stage neuro-pathic pain | Increasing histamine release, demyelination, PKC and RhoA-ROCK-JNK signaling, Pro-liferation, calcium signaling, ATP release, ERK signaling, early stage neuropathic pain | See references (reviews) | LPAR1 | (Blaho and Hla, 2011; Ueda, 2011) | |
Ca, calcium; CCL, chemokine ligand; CXCR1, C-X-C chemokine receptor type 1; DRGs, dorsal root ganglia; ELISA, enzyme-linked immunosorbent assay; ERK, extracellular-signal regulated kinase; IHC, immunohistochemistry; IL, interleukin; iPLA2, calcium-independent phospholipase 2; KD, knockdown; LPA, lysophosphatidic acid; LPC, lysophosphatidylcholine; LTP, long-term potentiation; MTT, 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; sEPSCs, spontaneous excitatory post synaptic currents; TGF, transforming growth factor; NPD1, neuroprotectin D1; S1P, sphingosine-1 phosphate; S1PR1, S1P receptor 1; DHA, docosahexaenoic acid; TNF, tumor necrosis factor; LPAR, lysophosphatidic acid receptor; TRPM8, transient receptor potential melastatin ion channel 8; ROCK, Rho-associated, coiled-coil-containing protein kinase; PKC, protein kinase C; GPR, G-protein coupled receptor.