A lipid gate for the peripheral control of pain

Journal of Neuroscience

Volumn 34, Issue 46, 2014, Pages 15184-15191

  Piomelli, Daniele ^a,b   Hohmann, Andrea G ^c   Seybold, Virginia ^d   Hammock, Bruce D ^e  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

^c INDIANA UNIVERSITY   (United States)

^d UNIVERSITY OF MINNESOTA   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

13 HYDROXYOCTADECENOIC ACID; ACYLGLYCEROL LIPASE; ANANDAMIDE; ARACHIDONIC ACID; CISPLATIN; CYTOCHROME P450; ENDOCANNABINOID; FATTY ACID; LYSOPHOSPHATIDIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; POLYUNSATURATED FATTY ACID; PROSTAGLANDIN E2; UNCLASSIFIED DRUG; VANILLOID RECEPTOR 1; VANILLOID RECEPTOR AGONIST; CANNABINOID RECEPTOR; CANNABINOID RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA;

AEROBIC METABOLISM; ARTICLE; ENZYME ACTIVITY; FATTY ACID METABOLISM; GENETIC TRANSCRIPTION; HUMAN; HYPERALGESIA; INFLAMMATION; MEDIATOR RELEASE; NERVE INJURY; NEUROPATHIC PAIN; NOCICEPTION; NOCICEPTIVE PAIN; NONHUMAN; PAIN RECEPTOR; PROTEIN EXPRESSION; SENSORY GATING; TISSUE INJURY; AGONISTS; ANIMAL; METABOLISM; PAIN; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; CANNABINOID RECEPTOR AGONISTS; ENDOCANNABINOIDS; HUMANS; HYPERALGESIA; INFLAMMATION; PAIN; PPAR ALPHA; RECEPTORS, CANNABINOID;

EID: 84909952250     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.3475-14.2014     Document Type: Article

References (82)

1. Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin CE, Brenner GJ, Rubino T, Michalski CW, Marsicano G, Monory K, Mackie K, Marian C, Batkai S, Parolaro D, Fischer MJ, Reeh P, Kunos G, Kress M, Lutz B, Woolf CJ, et al. (2007) Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nat Neurosci 10: 870–879.CrossRef Medline
2. Akopian AN, Ruparel NB, Jeske NA, Patwardhan A, Hargreaves KM (2009) Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia. Trends Pharmacol Sci 30:79–84.CrossRef Medline
3. Appiah KK, Blat Y, Robertson BJ, Pearce BC, Pedicord DL, Gentles RG, Yu XC, Mseeh F, Nguyen N, Swaffield JC, Harden DG, Westphal RS, Banks MN, O’Connell JC (2014) Identification of small molecules that selectively inhibit diacylglycerol lipase-alpha activity. J Biomol Screen 19:595-605.CrossRef Medline
4. Cain DM, Wacnik PW, Eikmeier L, Beitz A, Wilcox GL, Simone DA (2001) Functional interactions between tumor and peripheral nerve in a model of cancer pain in the mouse. Pain Med 2:15–23.CrossRef Medline
5. Calignano A, La Rana G, Giuffrida A, Piomelli D (1998) Control of pain initiation by endogenous cannabinoids. Nature 394:277–281.CrossRef Medline
6. Clapper JR, Moreno-Sanz G, Russo R, Guijarro A, Vacondio F, Duranti A, Tontini A, Sanchini S, Sciolino NR, Spradley JM, Hohmann AG, Calignano A, Mor M, Tarzia G, Piomelli D (2010) Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat Neurosci 13:1265–1270.CrossRef Medline
7. Deng L, Guindon J, Cornett BL, Makriyannis A, Mackie K, Hohmann AG (2014) Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal. Biol Psychiatry. Advance online publication. Retrieved Apr 25, 2014. doi: 10.1016/j.biopsych.2014.04.009.CrossRef Medline
8. Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W (1996) The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 384:39–43.CrossRef Medline
9. Dhopeshwarkar A, Mackie K (2014) CB2 cannabinoid receptors as a therapeutic target: what does the future hold? Mol Pharmacol 86:430–437.CrossRef Medline
10. Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D (2002) Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci U S A 99:10819-10824.CrossRef Medline
11. DiPatrizio NV, Astarita G, Schwartz G, Li X, Piomelli D (2011) Endocannabinoid signal in the gut controls dietary fat intake. Proc Natl Acad Sci U S A 108:12904-12908.CrossRef Medline
12. Ferreira SH (1972) Prostaglandins, aspirin-like drugs and analgesia. Nat New Biol 240:200-203.CrossRef Medline
13. Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodríguez De Fonseca F, Rosengarth A, Luecke H, Di Giacomo B, Tarzia G, Piomelli D (2003) Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425:90-93.CrossRef Medline
14. Fu J, Bottegoni G, Sasso O, Bertorelli R, Rocchia W, Masetti M, Guijarro A, Lodola A, Armirotti A, Garau G, Bandiera T, Reggiani A, Mor M, Cavalli A, Piomelli D (2012) A catalytically silent FAAH-1 variant drives anandamide transport in neurons. Nat Neurosci 15:64–69.CrossRef Medline
15. Gatta L, Piscitelli F, Giordano C, Boccella S, Lichtman A, Maione S, Di Marzo V (2012) Discovery of prostamide F2alpha and its role in inflammatory pain and dorsal horn nociceptive neuron hyperexcitability. PLoS One 7:e31111.CrossRef Medline
16. Gervois P, Mansouri RM (2012) PPARalpha as a therapeutic target in inflammation-associated diseases. Expert Opin Ther Targets 16:1113-1125.CrossRef Medline
17. Gregg LC, Jung KM, Spradley JM, Nyilas R, Suplita RL II, Zimmer A, Watanabe M, Mackie K, Katona I, Piomelli D, Hohmann AG (2012) Activation of type 5 metabotropic glutamate receptors and diacylglycerol lipase-alpha initiates 2-arachidonoylglycerol formation and endocannabinoid-mediated analgesia. J Neurosci 32:9457–9468.CrossRef Medline
18. Guedes AG, Morisseau C, Sole A, Soares JH, Ulu A, Dong H, Hammock BD (2013) Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Vet Anaesth Analg 40:440–448.CrossRef Medline
19. Guindon J, Hohmann AG (2008) A physiological role for endocannabinoidderived products of cyclooxygenase-2-mediated oxidative metabolism. Br J Pharmacol 153:1341–1343.CrossRef Medline
20. Guindon J, Hohmann AG (2009) The endocannabinoid system and pain. CNS Neurol Disord Drug Targets 8:403-421.CrossRef Medline
21. Guindon J, Hohmann AG (2011) The endocannabinoid system and cancer: therapeutic implication. Br J Pharmacol 163:1447–1463.CrossRef Medline
22. Guindon J, Lai Y, Takacs SM, Bradshaw HB, Hohmann AG (2013) Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment. Pharmacol Res 67:94-109.CrossRef Medline
23. Herkenham M (1991) Characterization and localization of cannabinoid receptors in brain: an in vitro technique using slide-mounted tissue sections. NIDA Res Monogr 112:129-145. Medline
24. Hermanson DJ, Hartley ND, Gamble-George J, Brown N, Shonesy BC, Kingsley PJ, Colbran RJ, Reese J, Marnett LJ, Patel S (2013) Substrateselective COX-2 inhibition decreases anxiety via endocannabinoid activation. Nat Neurosci 16:1291–1298.CrossRef Medline
25. Hiura A, Sakamoto Y (1987) Quantitative estimation of the effects of capsaicin on the mouse primary sensory neurons. Neurosci Lett 76:101–106.CrossRef Medline
26. Hohmann AG, Herkenham M (1999) Cannabinoid receptors undergo axonal flow in sensory nerves. Neuroscience 92:1171–1175.CrossRef Medline
27. Hohmann AG, Suplita RL, Bolton NM, Neely MH, Fegley D, Mangieri R, Krey JF, Walker JM, Holmes PV, Crystal JD, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2005) An endocannabinoid mechanism for stress-induced analgesia. Nature 435:1108-1112.CrossRef Medline
28. Inceoglu B, Wagner K, Schebb NH, Morisseau C, Jinks SL, Ulu A, Hegedus C, Rose T, Brosnan R, Hammock BD (2011) Analgesia mediated by soluble epoxide hydrolase inhibitors is dependent on cAMP. Proc Natl Acad Sci U S A 108:5093–5097.CrossRef Medline
29. Inceoglu B, Wagner KM, Yang J, Bettaieb A, Schebb NH, Hwang SH, Morisseau C, Haj FG, Hammock BD (2012) Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes. Proc Natl Acad Sci U S A 109:11390-11395.CrossRef Medline
30. Inceoglu B, Zolkowska D, Yoo HJ, Wagner KM, Yang J, Hackett E, Hwang SH, Lee KS, Rogawski MA, Morisseau C, Hammock BD (2013) Epoxy fatty acids and inhibition of the soluble epoxide hydrolase selectively modulate GABA mediated neurotransmission to delay onset of seizures. PLoS One 8:e80922.CrossRef Medline
31. Kathuria S, Gaetani S, Fegley D, Valiño F, Duranti A, Tontini A, Mor M, Tarzia G, La Rana G, Calignano A, Giustino A, Tattoli M, Palmery M, Cuomo V, Piomelli D (2003) Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 9:76–81.CrossRef Medline
32. Khasabova IA, Stucky CL, Harding-Rose C, Eikmeier L, Beitz AJ, Coicou LG, Hanson AE, Simone DA, Seybold VS (2007) Chemical interactions between fibrosarcoma cancer cells and sensory neurons contribute to cancer pain. J Neurosci 27:10289-10298.CrossRef Medline
33. Khasabova IA, Khasabov SG, Harding-Rose C, Coicou LG, Seybold BA, Lindberg AE, Steevens CD, Simone DA, Seybold VS (2008) A decrease in anandamide signaling contributes to the maintenance of cutaneous mechanical hyperalgesia in a model of bone cancer pain. J Neurosci 28: 11141–11152.CrossRef Medline
34. Khasabova IA, Xiong Y, Coicou LG, Piomelli D, Seybold V (2012) Peroxisome proliferator-activated receptor alpha mediates acute effects of palmitoylethanolamide on sensory neurons. J Neurosci 32:12735–12743.CrossRef Medline
35. Khasabova IA, Holman M, Morse T, Burlakova N, Coicou L, Harding-Rose C, Simone DA, Seybold VS (2013) Increased anandamide uptake by sensory neurons contributes to hyperalgesia in a model of cancer pain. Neurobiol Dis 58:19-28.CrossRef Medline
36. Kostadinova R, Wahli W, Michalik L (2005) PPARs in diseases: control mechanisms of inflammation. Curr Med Chem 12:2995–3009.CrossRef Medline
37. Long JZ, Nomura DK, Cravatt BF (2009) Characterization of monoacylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolism. Chem Biol 16:744-753.CrossRef Medline
38. LoVerme J, La Rana G, Russo R, Calignano A, Piomelli D (2005) The search for the palmitoylethanolamide receptor. Life Sci 77:1685–1698.CrossRef Medline
39. LoVerme J, Russo R, La Rana G, Fu J, Farthing J, Mattace-Raso G, Meli R, Hohmann A, Calignano A, Piomelli D (2006) Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha. J Pharmacol Exp Ther 319:1051–1061.CrossRef Medline
40. Mantyh PW, Clohisy DR, Koltzenburg M, Hunt SP (2002) Molecular mechanisms of cancer pain. Nat Rev Cancer 2:201–209.CrossRef Medline
41. Marrs WR, Blankman JL, Horne EA, Thomazeau A, Lin YH, Coy J, Bodor AL, Muccioli GG, Hu SS, Woodruff G, Fung S, Lafourcade M, Alexander JP, Long JZ, Li W, Xu C, Möller T, Mackie K, Manzoni OJ, Cravatt BF, et al. (2010) The serine hydrolase ABHD6 controls the accumulation and efficacy of 2-AG at cannabinoid receptors. Nat Neurosci 13:951–957.CrossRef Medline
42. Mercadante S (1999) Pain treatment and outcomes for patients with advanced cancer who receive follow-up care at home. Cancer 85:1849-1858.CrossRef Medline
43. Mitrirattanakul S, Ramakul N, Guerrero AV, Matsuka Y, Ono T, Iwase H, Mackie K, Faull KF, Spigelman I (2006) Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain. Pain 126:102–114.CrossRef Medline
44. Moreno-Sanz G, Barrera B, Guijarro A, d’Elia I, Otero JA, Alvarez AI, Bandiera T, Merino G, Piomelli D (2011) The ABC membrane transporter ABCG2 prevents access of FAAH inhibitor URB937 to the central nervous system. Pharmacol Res 64:359-363.CrossRef Medline
45. Morisseau C, Hammock BD (2013) Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol 53:37–58.CrossRef Medline
46. Morisseau C, Inceoglu B, Schmelzer K, Tsai HJ, Jinks SL, Hegedus CM, Hammock BD (2010) Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids. J Lipid Res 51:3481–3490.CrossRef Medline
47. Nackley AG, Suplita RL II, Hohmann AG (2003a) A peripheral cannabinoid mechanism suppresses spinal fos protein expression and pain behavior in a rat model of inflammation. Neuroscience 117:659–670.CrossRef Medline
48. Nackley AG, Makriyannis A, Hohmann AG (2003b) Selective activation of cannabinoid CB(2) receptors suppresses spinal fos protein expression and pain behavior in a rat model of inflammation. Neuroscience 119:747–757.CrossRef Medline
49. Nackley AG, Zvonok AM, Makriyannis A, Hohmann AG (2004) Activation of cannabinoid CB2 receptors suppresses C-fiber responses and windup in spinal wide dynamic range neurons in the absence and presence of inflammation. J Neurophysiol 92:3562–3574.CrossRef Medline
50. O’Sullivan SE, Kendall DA (2010) Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology 215:611-616.CrossRef Medline
51. Panigrahy D, Kalish BT, Huang S, Bielenberg DR, Le HD, Yang J, Edin ML, Lee CR, Benny O, Mudge DK, Butterfield CE, Mammoto A, Mammoto T, Inceoglu B, Jenkins RL, Simpson MA, Akino T, Lih FB, Tomer KB, Ingber DE, et al. (2013) Epoxyeicosanoids promote organ and tissue regeneration. Proc Natl Acad Sci U S A 110:13528-13533.CrossRef Medline
52. Pearce RJ, Duchen MR (1994) Differential expression of membrane currents in dissociated mouse primary sensory neurons. Neuroscience 63: 1041–1056.CrossRef Medline
53. Piomelli D, Sasso O (2014) Peripheral gating of pain signals by endogenous lipid mediators. Nat Neurosci 17:164-174.CrossRef Medline
54. Pisanti S, Picardi P, D’Alessandro A, Laezza C, Bifulco M (2013) The endocannabinoid signaling system in cancer. Trends Pharmacol Sci 34:273-282.CrossRef Medline
55. Price TJ, Patwardhan A, Akopian AN, Hargreaves KM, Flores CM (2004) Modulation of trigeminal sensory neuron activity by the dual cannabinoidvanilloid agonists anandamide, N-arachidonoyl-dopamine and arachidonyl-2- chloroethylamide. Br J Pharmacol 141:1118–1130.CrossRef Medline
56. Rahman IA, Tsuboi K, Uyama T, Ueda N (2014) New players in the fatty acyl ethanolamide metabolism. Pharmacol Res 86C:1–10.CrossRef Medline
57. Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, Kendall DA, Scammell BE, Reeve AJ, Chapman V (2008) Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 10:R43.CrossRef Medline
58. Richardson JD, Kilo S, Hargreaves KM (1998) Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors. Pain 75:111–119.CrossRef Medline
59. Ruiz-Medina J, Flores JA, Tasset I, Tunez I, Valverde O, Fernandez-Espejo E (2012) Alteration of neuropathic and visceral pain in female C57BL/6J mice lacking the PPAR-alpha gene. Psychopharmacology (Berl) 222:477-488.CrossRef Medline
60. Sagar DR, Kelly S, Millns PJ, O’Shaughnessey CT, Kendall DA, Chapman V (2005) Inhibitory effects of CB1 and CB2 receptor agonists on responses of DRG neurons and dorsal horn neurons in neuropathic rats. Eur J Neurosci 22:371–379.CrossRef Medline
61. Sasso O, Bertorelli R, Bandiera T, Scarpelli R, Colombano G, Armirotti A, Moreno-Sanz G, Reggiani A, Piomelli D (2012) Peripheral FAAH inhibition causes profound antinociception and protects against indomethacininduced gastric lesions. Pharmacol Res 65:553–563.CrossRef Medline
62. Sasso O, Moreno-Sanz G, Martucci C, Realini N, Dionisi M, Mengatto L, Duranti A, Tarozzo G, Tarzia G, Mor M, Bertorelli R, Reggiani A, Piomelli D (2013) Antinociceptive effects of the N-acylethanolamine acid amidase inhibitor ARN077 in rodent pain models. Pain 154:350-360.CrossRef Medline
63. Schmelzer KR, Kubala L, Newman JW, Kim IH, Eiserich JP, Hammock BD (2005) Soluble epoxide hydrolase is a therapeutic target for acute inflammation. Proc Natl Acad Sci U S A 102:9772–9777.CrossRef Medline
64. Schmelzer KR, Inceoglu B, Kubala L, Kim IH, Jinks SL, Eiserich JP, Hammock BD (2006) Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors. Proc Natl Acad Sci U S A 103:13646-13651.CrossRef Medline
65. Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML, Clohisy DR, Mantyh PW (1999) Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J Neurosci 19:10886-10897.
66. Medline Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8:349-361.CrossRef Medline
67. Shen HC, Hammock BD (2012) Discovery of inhibitors of soluble epoxide hydrolase: a target with multiple potential therapeutic indications. J Med Chem 55:1789-1808.CrossRef Medline
68. Solorzano C, Zhu C, Battista N, Astarita G, Lodola A, Rivara S, Mor M, Russo R, Maccarrone M, Antonietti F, Duranti A, Tontini A, Cuzzocrea S, Tarzia G, Piomelli D (2009) Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation. Proc Natl Acad Sci U S A 106:20966-20971.CrossRef Medline
69. Spradley JM, Guindon J, Hohmann AG (2010) Inhibitors of monoacylglycerol lipase, fatty-acid amide hydrolase and endocannabinoid transport differentially suppress capsaicin-induced behavioral sensitization through peripheral endocannabinoid mechanisms. Pharmacol Res 62:249–258.CrossRef Medline
70. Stella N, Schweitzer P, Piomelli D (1997) A second endogenous cannabinoid that modulates long-term potentiation. Nature 388:773–778.CrossRef Medline
71. Svízenska´ IH, Brázda V, Klusáková I, Dubovy´ P (2013) Bilateral changes of cannabinoid receptor type 2 protein and mRNA in the dorsal root ganglia of a rat neuropathic pain model. J Histochem Cytochem 61:529-547.CrossRef Medline
72. Taylor BK, Dadia N, Yang CB, Krishnan S, Badr M (2002) Peroxisome proliferator-activated receptor agonists inhibit inflammatory edema and hyperalgesia. Inflammation 26:121–127.CrossRef Medline
73. Ueda N, Tsuboi K, Uyama T (2013) Metabolism of endocannabinoids and related N-acylethanolamines: canonical and alternative pathways. FEBS J 280:1874-1894.CrossRef Medline
74. Ulu A, Stephen Lee KS, Miyabe C, Yang J, Hammock BG, Dong H, Hammock BD (2014) An omega-3 epoxide of docosahexaenoic acid lowers blood pressure in angiotensin-II-dependent hypertension. J Cardiovasc Pharmacol 64:87–99.CrossRef Medline
75. Wacnik PW, Eikmeier LJ, Ruggles TR, Ramnaraine ML, Walcheck BK, Beitz AJ, Wilcox GL (2001) Functional interactions between tumor and peripheral nerve: morphology, algogen identification, and behavioral characterization of a new murine model of cancer pain. J Neurosci 21:9355-9366.
76. Medline Wacnik PW, Baker CM, Herron MJ, Kren BT, Blazar BR, Wilcox GL, Hordinsky MK, Beitz AJ, Ericson ME (2005) Tumor-induced mechanical hyperalgesia involves CGRP receptors and altered innervation and vascularization of DsRed2 fluorescent hindpaw tumors. Pain 115:95–106.CrossRef Medline
77. Wagner K, Inceoglu B, Hammock BD (2011) Soluble epoxide hydrolase inhibition, epoxygenated fatty acids and nociception. Prostaglandins Other Lipid Mediat 96:76–83.CrossRef Medline
78. Wotherspoon G, Fox A, McIntyre P, Colley S, Bevan S, Winter J (2005) Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons. Neuroscience 135:235–245.CrossRef Medline
79. Xu D, Li N, He Y, Timofeyev V, Lu L, Tsai HJ, Kim IH, Tuteja D, Mateo RK, Singapuri A, Davis BB, Low R, Hammock BD, Chiamvimonvat N (2006) Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors. Proc Natl Acad Sci U S A 103:18733–18738.CrossRef Medline
80. Zhang G, Panigrahy D, Mahakian LM, Yang J, Liu JY, Stephen Lee KS, Wettersten HI, Ulu A, Hu X, Tam S, Hwang SH, Ingham ES, Kieran MW, Weiss RH, Ferrara KW, Hammock BD (2013) Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci U S A 110:6530–6535.CrossRef Medline
81. Zhang G, Kodani S, Hammock BD (2014) Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer. Prog Lipid Res 53:108-123.CrossRef Medline
82. Zhu C, Solorzano C, Sahar S, Realini N, Fung E, Sassone-Corsi P, Piomelli D (2011) Proinflammatory stimuli control N-acylphosphatidylethanolamine-specific phospholipase D expression in macrophages. Mol Pharmacol 79:786–792.CrossRef Medline