33. Harayama T, Shindou H, Ogasawara R, Suwabe A, Shimizu T (2008) Identification of a novel noninflammatory biosynthetic pathway of platelet- activating factor. J Biol Chem 283: 11097–11106. 34. Kihara Y, Yanagida K, Masago K, Kita Y, Hishikawa D, et al. (2008) Platelet- activating factor production in the spinal cord of experimental allergic encephalomyelitis mice via the group IVA cytosolic phospholipase A2-lyso- PAFAT axis. J Immunol 181: 5008–5014. 35. Ishii S, Shimizu T (2000) Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Prog Lipid Res 39: 41–82. 36. Ishii S, Kuwaki T, Nagase T, Maki K, Tashiro F, et al. (1998) Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor. J Exp Med 187: 1779–1788. 37. Tsuda M, Ishii S, Masuda T, Hasegawa S, Nakamura K, et al. (2007) Reduced pain behaviors and extracellular signal-related protein kinase activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet- activating factor receptor. J Neurochem 102: 1658–1668. 38. Schafers M, Geis C, Svensson CI, Luo ZD, Sommer C (2003) Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Eur J Neurosci 17: 791–804. 39. Kihara Y, Ishii S, Kita Y, Toda A, Shimada A, et al. (2005) Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor. J Exp Med 202: 853–863. 40. Fernandes ES, Passos GF, Campos MM, de Souza GE, Fittipaldi JF, et al. (2005) Cytokines and neutrophils as important mediators of platelet-activating factor- induced kinin B1 receptor expression. Br J Pharmacol 146: 209–216. 41. Hefferan MP, O’Rielly DD, Loomis CW (2003) Inhibition of spinal prostaglandin synthesis early after L5/L6 nerve ligation prevents the development of prostaglandin-dependent and prostaglandin-independent allo- dynia in the rat. Anesthesiology 99: 1180–1188. 42. Zhu X, Eisenach JC (2003) Cyclooxygenase-1 in the spinal cord is altered after peripheral nerve injury. Anesthesiology 99: 1175–1179. 43. Zhao Z, Chen SR, Eisenach JC, Busija DW, Pan HL (2000) Spinal cyclooxygenase-2 is involved in development of allodynia after nerve injury in rats. Neuroscience 97: 743–748. 44. Kost RG, Straus SE (1996) Postherpetic neuralgia–pathogenesis, treatment, and prevention. N Engl J Med 335: 32–42. 45. Samuelsson B (1983) Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 220: 568–575. 46. Levine JD, Lau W, Kwiat G, Goetzl EJ (1984) Leukotriene B4 produces hyperalgesia that is dependent on polymorphonuclear leukocytes. Science 225: 743–745. 47. Levine JD, Lam D, Taiwo YO, Donatoni P, Goetzl EJ (1986) Hyperalgesic properties of 15-lipoxygenase products of arachidonic acid. Proc Natl Acad Sci U S A 83: 5331–5334. 48. Doi K, Okamoto K, Negishi K, Suzuki Y, Nakao A, et al. (2006) Attenuation of folic acid-induced renal inflammatory injury in platelet-activating factor receptor-deficient mice. Am J Pathol 168: 1413–1424. 49. Scholz J, Woolf CJ (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10: 1361–1368. PAFR and Neuropathic Pain 50. Marchand F, Perretti M, McMahon SB (2005) Role of the immune system in chronic pain. Nat Rev Neurosci 6: 521–532. 51. Mantyh PW (2006) Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci 7: 797–809. 52. Moalem G, Tracey DJ (2006) Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev 51: 240–264. 53. Schafers M, Geis C, Brors D, Yaksh TL, Sommer C (2002) Anterograde transport of tumor necrosis factor-alpha in the intact and injured rat sciatic nerve. J Neurosci 22: 536–545. 54. Li H, Xie W, Strong JA, Zhang JM (2007) Systemic antiinflammatory corticosteroid reduces mechanical pain behavior, sympathetic sprouting, and elevation of proinflammatory cytokines in a rat model of neuropathic pain. Anesthesiology 107: 469–477. 55. Uceyler N, Tscharke A, Sommer C (2007) Early cytokine expression in mouse sciatic nerve after chronic constriction nerve injury depends on calpain. Brain Behav Immun 21: 553–560. 56. Sacerdote P, Franchi S, Trovato AE, Valsecchi AE, Panerai AE, et al. (2008) Transient early expression of TNF-alpha in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy. Neurosci Lett 436: 210–213. 57. Jin X, Gereau RWt (2006) Acute p38-mediated modulation of tetrodotoxin- resistant sodium channels in mouse sensory neurons by tumor necrosis factor- alpha. J Neurosci 26: 246–255. 58. Liu L, Yang TM, Liedtke W, Simon SA (2006) Chronic IL-1beta signaling potentiates voltage-dependent sodium currents in trigeminal nociceptive neurons. J Neurophysiol 95: 1478–1490. 59. Elmes SJ, Millns PJ, Smart D, Kendall DA, Chapman V (2004) Evidence for biological effects of exogenous LPA on rat primary afferent and spinal cord neurons. Brain Res 1022: 205–213. 60. Renback K, Inoue M, Ueda H (1999) Lysophosphatidic acid-induced, pertussis toxin-sensitive nociception through a substance P release from peripheral nerve endings in mice. Neurosci Lett 270: 59–61. 61. Hasegawa S, Kohro Y, Tsuda M, Inoue K (2009) Activation of cytosolic phospholipase A2 in dorsal root ganglion neurons by Ca2+/calmodulin- dependent protein kinase II after peripheral nerve injury. Mol Pain 5: 22. 62. Lindsberg PJ, Hallenbeck JM, Feuerstein G (1991) Platelet-activating factor in stroke and brain injury. Ann Neurol 30: 117–129. 63. Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50: 355–363. 64. Tsuda M, Shigemoto-Mogami Y, Koizumi S, Mizokoshi A, Kohsaka S, et al. (2003) P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424: 778–783. 65. Tsuda M, Masuda T, Kitano J, Shimoyama H, Tozaki-Saitoh H, et al. (2009) IFN-gamma receptor signaling mediates spinal microglia activation driving neuropathic pain. Proc Natl Acad Sci U S A 106: 8032–8037. 66. Obata K, Yamanaka H, Kobayashi K, Dai Y, Mizushima T, et al. (2004) Role of mitogen-activated protein kinase activation in injured and intact primary afferent neurons for mechanical and heat hypersensitivity after spinal nerve ligation. J Neurosci 24: 10211–10222. PLoS ONE | www.plosone.org 11 May 2010 | Volume 5 | Issue 5 | e10467