Prostanoids and inflammatory pain.

Prostanoids play pivotal roles in inflammation and pain. Cyclooxygenase (COX) inhibitors, the nonsteroidal anti-inflammatory drugs (NSAIDs), depress prostanoid formation and are widely used to treat inflammatory pain. However, their therapeutic benefit is offset by serious side-effects, primarily gastrointestinal and cardiovascular complications. Pathway elements downstream of the COX enzymes, particularly the terminal synthases and receptors of prostaglandin E2, have been proposed as alternative targets for the development of novel NSAID like drugs. Here, we summarize the current knowledge on the roles of individual prostanoids in modulating inflammatory pain.

[1]  H. Schaible,et al.  Prostaglandins and cycloxygenases in the spinal cord , 2001, Progress in Neurobiology.

[2]  M. Vasko,et al.  Prostacyclin enhances the evoked-release of substance P and calcitonin gene-related peptide from rat sensory neurons , 1994, Brain Research.

[3]  K. Omote,et al.  The Effects of Peripheral Administration of a Novel Selective Antagonist for Prostaglandin E Receptor Subtype EP1, ONO-8711, in a Rat Model of Postoperative Pain , 2001, Anesthesia and analgesia.

[4]  S. Narumiya,et al.  In situ hybridization studies of prostacyclin receptor mRNA expression in various mouse organs , 1995, British journal of pharmacology.

[5]  O. Yuge,,et al.  Intrathecally administered COX-2 but not COX-1 or COX-3 inhibitors attenuate streptozotocin-induced mechanical hyperalgesia in rats. , 2007, European journal of pharmacology.

[6]  Gerd Geisslinger,et al.  Cyclooxygenase‐independent actions of cyclooxygenase inhibitors , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  Tetsuya Abe,et al.  Membrane-associated prostaglandin E synthase-1 is required for neuropathic pain , 2004, Neuroreport.

[8]  M. Tominaga,et al.  Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins , 2005, Molecular pain.

[9]  S. Narumiya,et al.  Prostaglandin D2 as a mediator of allergic asthma. , 2000, Science.

[10]  P. Isakson,et al.  Characterization of a monoclonal antibody that neutralizes the activity of prostaglandin E2. , 1995, Journal of immunology.

[11]  K. Scholich,et al.  Is mPGES-1 a promising target for pain therapy? , 2006, Trends in pharmacological sciences.

[12]  Y. Urade,et al.  Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  O. Hayaishi,et al.  Prostaglandin D2 inhibits prostaglandin E2-induced allodynia in conscious mice. , 1996, The Journal of pharmacology and experimental therapeutics.

[14]  Steve Rowland,et al.  Discovery of 4-[1-[([1-[4-(trifluoromethyl)benzyl]-1H-indol-7-yl]carbonyl)amino]cyclopropyl]benzoic acid (MF-766), a highly potent and selective EP4 antagonist for treating inflammatory pain. , 2010, Bioorganic & medicinal chemistry letters.

[15]  J. de Belleroche,et al.  Carrageenan‐induced hyperalgesia is associated with increased cyclo‐oxygenase‐2 expression in spinal cord , 1997, Neuroreport.

[16]  C. Woolf,et al.  Central sensitization: a generator of pain hypersensitivity by central neural plasticity. , 2009, The journal of pain : official journal of the American Pain Society.

[17]  S. Narumiya,et al.  Inhibitory effect of a prostaglandin E receptor subtype EP(1) selective antagonist, ONO-8713, on development of azoxymethane-induced aberrant crypt foci in mice. , 2000, Cancer letters.

[18]  C. Maihöfner,et al.  Localization and regulation of cyclo-oxygenase-1 and -2 and neuronal nitric oxide synthase in mouse spinal cord , 2000, Neuroscience.

[19]  N. Méthot,et al.  MF63 [2-(6-Chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile], a Selective Microsomal Prostaglandin E Synthase-1 Inhibitor, Relieves Pyresis and Pain in Preclinical Models of Inflammation , 2008, Journal of Pharmacology and Experimental Therapeutics.

[20]  S. Heller,et al.  Protease-Activated Receptors: Mechanisms by Which Proteases Sensitize TRPV Channels to Induce Neurogenic Inflammation and Pain -- TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades , 2006 .

[21]  S. Yoshikawa,et al.  Functional role of prostacyclin receptor in rat dorsal root ganglion neurons , 2005, Neuroscience Letters.

[22]  F. Cunha,et al.  The role of NaV1.8 sodium channel in the maintenance of chronic inflammatory hypernociception , 2005, Neuroscience Letters.

[23]  P. Isakson,et al.  Effect of COX-1 and COX-2 inhibition on induction and maintenance of carrageenan-evoked thermal hyperalgesia in rats. , 1998, The Journal of pharmacology and experimental therapeutics.

[24]  Adam Sapirstein,et al.  Interleukin-1β-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity , 2001, Nature.

[25]  H. Rang,et al.  Effect of bradykinin and prostaglandins on the release of calcitonin gene‐related peptide‐like immunoreactivity from the rat spinal cord in vitro , 1993, British journal of pharmacology.

[26]  Y. Murata,et al.  CJ-023,423, a Novel, Potent and Selective Prostaglandin EP4 Receptor Antagonist with Antihyperalgesic Properties , 2007, Journal of Pharmacology and Experimental Therapeutics.

[27]  J. Francischi,et al.  Selective inhibitors of cyclo‐oxygenase‐2 (COX‐2) induce hypoalgesia in a rat paw model of inflammation , 2002, British journal of pharmacology.

[28]  R. Breyer,et al.  Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. , 2004, Pharmacology & therapeutics.

[29]  L. Audoly,et al.  The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis. , 2002, The Journal of clinical investigation.

[30]  J. Eisenach,et al.  Cyclooxygenase-1 in the Spinal Cord Is Altered after Peripheral Nerve Injury , 2003, Anesthesiology.

[31]  J. Lapointe,et al.  Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Makoto Murakami,et al.  Prostaglandin E synthase, a terminal enzyme for prostaglandin E2 biosynthesis. , 2005, Journal of biochemistry and molecular biology.

[33]  I. Chessell,et al.  The discovery of 6-[2-(5-chloro-2-{[(2,4-difluorophenyl)methyl]oxy}phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid, GW848687X, a potent and selective prostaglandin EP1 receptor antagonist for the treatment of inflammatory pain. , 2007, Bioorganic & medicinal chemistry letters.

[34]  M. Koyama,et al.  Expression of prostaglandin EP2 receptor mRNA in the rat spinal cord. , 1997, Life sciences.

[35]  R. Langenbach,et al.  Cyclooxygenase knockout mice: models for elucidating isoform-specific functions. , 1999, Biochemical pharmacology.

[36]  T. Kumazawa,et al.  EP receptor subtypes implicated in the PGE2-induced sensitization of polymodal receptors in response to bradykinin and heat. , 1996, Journal of neurophysiology.

[37]  A. Kawabata Prostaglandin E2 and pain--an update. , 2011, Biological & pharmaceutical bulletin.

[38]  G. FitzGerald,et al.  Microsomal prostaglandin E synthase‐1 inhibition in cardiovascular inflammatory disease , 2008, Journal of internal medicine.

[39]  C. Asante,et al.  The Cell and Molecular Basis of Mechanical, Cold, and Inflammatory Pain , 2008, Science.

[40]  C. Saper,et al.  COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice. , 2009, The Journal of clinical investigation.

[41]  S. Narumiya,et al.  Comparison of nociceptive behavior in prostaglandin E, F, D, prostacyclin and thromboxane receptor knockout mice , 2009, European journal of pain.

[42]  S. Mutoh,et al.  Role of cyclooxygenase-2, but not cyclooxygenase-1, on type II collagen-induced arthritis in DBA/1J mice. , 2003, Biochemical pharmacology.

[43]  S. Giblett,et al.  Prostanoids synthesized by cyclo‐oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability , 1997, British journal of pharmacology.

[44]  G. FitzGerald,et al.  Genetic and pharmacological analysis of prostanoid receptor function. , 2001, The Journal of clinical investigation.

[45]  M. Vasko,et al.  Prostaglandin E2 enhances bradykinin-stimulated release of neuropeptides from rat sensory neurons in culture , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  T. Yaksh,et al.  Cyclooxygenase inhibition and the spinal release of prostaglandin E2 and amino acids evoked by paw formalin injection: a microdialysis study in unanesthetized rats , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  J. Levine,et al.  Role of a Ca2+-dependent slow afterhyperpolarization in prostaglandin E2-induced sensitization of cultured rat sensory neurons , 1996, Neuroscience Letters.

[48]  M. Nishizawa,et al.  Central nociceptive role of prostacyclin (IP) receptor induced by peripheral inflammation , 2002, Neuroreport.

[49]  T. Grosser,et al.  PROSTANOIDS IN HEALTH AND DISEASE , 1979 .

[50]  H Perrier,et al.  Rofecoxib [Vioxx, MK-0966; 4-(4'-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. , 1999, The Journal of pharmacology and experimental therapeutics.

[51]  M. Sekiguchi,et al.  Analgesic Effects of Prostaglandin E2 Receptor Subtype EP1 Receptor Antagonist: Experimental Study of Application of Nucleus Pulposus , 2011, Spine.

[52]  P. Beaulieu,et al.  Local interactions between anandamide, an endocannabinoid, and ibuprofen, a nonsteroidal anti-inflammatory drug, in acute and inflammatory pain , 2006, Pain.

[53]  S. Narumiya,et al.  Altered pain perception and inflammatory response in mice lacking prostacyclin receptor , 1997, Nature.

[54]  Discovery of a novel series of nonacidic benzofuran EP1 receptor antagonists. , 2011, Bioorganic & medicinal chemistry letters.

[55]  K. Omote,et al.  Role of Prostaglandin Receptor EP1 in the Spinal Dorsal Horn in Carrageenan-induced Inflammatory Pain , 2002, Anesthesiology.

[56]  C. Woolf,et al.  Pain: molecular mechanisms. , 2000, The journal of pain : official journal of the American Pain Society.

[57]  J. Lopshire,et al.  The cAMP Transduction Cascade Mediates the Prostaglandin E2 Enhancement of the Capsaicin-Elicited Current in Rat Sensory Neurons: Whole-Cell and Single-Channel Studies , 1998, The Journal of Neuroscience.

[58]  R. Riccio,et al.  Anti-inflammatory and analgesic activity of a novel inhibitor of microsomal prostaglandin E synthase-1 expression. , 2009, European journal of pharmacology.

[59]  F. Kojima,et al.  Prostaglandin E synthase in the pathophysiology of arthritis , 2005, Fundamental & clinical pharmacology.

[60]  S. Reddy,et al.  Prostaglandin Synthase-1 and Prostaglandin Synthase-2 Are Coupled to Distinct Phospholipases for the Generation of Prostaglandin D2 in Activated Mast Cells* , 1997, The Journal of Biological Chemistry.

[61]  S. Narumiya,et al.  Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype. , 2005, The Journal of clinical investigation.

[62]  K. Brune,et al.  Suppressed Injury-Induced Rise in Spinal Prostaglandin E2 Production and Reduced Early Thermal Hyperalgesia in iNOS-Deficient Mice , 2000, The Journal of Neuroscience.

[63]  Kazunari Nakao,et al.  Effect of prostanoid EP4 receptor antagonist, CJ-042,794, in rat models of pain and inflammation. , 2008, European journal of pharmacology.

[64]  H. Afif,et al.  Inhibition of interleukin-1beta-induced matrix metalloproteinases 1 and 13 production in human osteoarthritic chondrocytes by prostaglandin D2. , 2008, Arthritis and rheumatism.

[65]  R. Schuligoi,et al.  Role of cyclooxygenase-2 in gastric mucosal defense. , 2001, Life sciences.

[66]  James A. Clark,et al.  Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice1 , 2008, Journal of Immunology.

[67]  L. Audoly,et al.  A novel role of prostaglandin E2 in neuropathic pain , 2011, Glia.

[68]  M. Vasko,et al.  Prostaglandins suppress an outward potassium current in embryonic rat sensory neurons. , 1997, Journal of neurophysiology.

[69]  H. Wässle,et al.  GlyR α3: An Essential Target for Spinal PGE2-Mediated Inflammatory Pain Sensitization , 2004, Science.

[70]  L. Ballou,et al.  The genetic ablation of cyclooxygenase 2 prevents the development of autoimmune arthritis. , 2000, Arthritis and rheumatism.

[71]  D. Willoughby,et al.  Distribution of cyclooxygenase isoforms in murine chronic granulomatous inflammation. Implications for future anti‐inflammatory therapy , 1995, The Journal of pathology.

[72]  David Julius,et al.  Cellular and Molecular Mechanisms of Pain , 2009, Cell.

[73]  A. Naylor,et al.  Discovery of GSK345931A: An EP(1) receptor antagonist with efficacy in preclinical models of inflammatory pain. , 2009, Bioorganic & medicinal chemistry letters.

[74]  K. Seibert,et al.  Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[75]  C. Hay,et al.  Dexamethasone prevents the induction of COX-2 mRNA and prostaglandins in the lumbar spinal cord following intraplantar FCA in parallel with inhibition of oedema , 1998, Neuropharmacology.

[76]  C. Woolf,et al.  Direct Activation of Rat Spinal Dorsal Horn Neurons by Prostaglandin E2 , 2001, The Journal of Neuroscience.

[77]  S. Narumiya,et al.  Evidence for involvement of prostaglandin I2 as a major nociceptive mediator in acetic acid-induced writhing reaction: a study using IP-receptor disrupted mice. , 1999, Advances in experimental medicine and biology.

[78]  P. Clark,et al.  MF498 [N-{[4-(5,9-Diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl}-2-(2-methoxyphenyl)acetamide], a Selective E Prostanoid Receptor 4 Antagonist, Relieves Joint Inflammation and Pain in Rodent Models of Rheumatoid and Osteoarthritis , 2008, Journal of Pharmacology and Experimental Therapeutics.

[79]  T. Grosser,et al.  Emotion recollected in tranquility: lessons learned from the COX-2 saga. , 2010, Annual review of medicine.

[80]  M. Vasko,et al.  Prostaglandin E2 increases calcium conductance and stimulates release of substance P in avian sensory neurons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[81]  S. Narumiya,et al.  The DP receptor, allergic inflammation and asthma. , 2003, Prostaglandins, leukotrienes, and essential fatty acids.

[82]  W. Neupert,et al.  Peripheral noxious stimulation releases spinal PGE2 during the first phase in the formalin assay of the rat. , 1997, Life sciences.

[83]  C. Woolf,et al.  Prostaglandin E2 Receptor EP4 Contributes to Inflammatory Pain Hypersensitivity , 2006, Journal of Pharmacology and Experimental Therapeutics.

[84]  D. Riendeau,et al.  Prostacyclin Antagonism Reduces Pain and Inflammation in Rodent Models of Hyperalgesia and Chronic Arthritis , 2006, Journal of Pharmacology and Experimental Therapeutics.

[85]  M. Vasko,et al.  The cAMP transduction cascade mediates the PGE2‐induced inhibition of potassium currents in rat sensory neurones , 1999, The Journal of physiology.

[86]  J. Eisenach,et al.  Cyclooxygenase-1 in the spinal cord plays an important role in postoperative pain , 2003, Pain.

[87]  M. Breyer,et al.  Physiological regulation of cyclooxygenase-2 in the kidney. , 2001, American journal of physiology. Renal physiology.

[88]  Hyung-Suk Kim,et al.  Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration , 1995, Cell.

[89]  M. Marsala,et al.  Effect of spinal kainic acid receptor activation on spinal amino acid and prostaglandin E2 release in rat , 1996, Neuroscience.

[90]  L. Audoly,et al.  Redirection of Eicosanoid Metabolism in mPGES-1-deficient Macrophages* , 2005, Journal of Biological Chemistry.

[91]  K. Brune,et al.  Analgesic strategies beyond the inhibition of cyclooxygenases. , 2006, Trends in pharmacological sciences.

[92]  Lawrence J. Marnett,et al.  Cyclooxygenase-1-dependent Prostaglandin Synthesis Modulates Tumor Necrosis Factor-α Secretion in Lipopolysaccharide-challenged Murine Resident Peritoneal Macrophages* , 2004, Journal of Biological Chemistry.

[93]  Ying Yu,et al.  Vascular COX-2 Modulates Blood Pressure and Thrombosis in Mice , 2012, Science Translational Medicine.

[94]  C. Brenneis,et al.  Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient mice , 2007, Journal of cellular and molecular medicine.

[95]  J. Levine,et al.  Modulation of TTX-R INa by PKC and PKA and Their Role in PGE2-Induced Sensitization of Rat Sensory Neurons In Vitro , 1998, The Journal of Neuroscience.

[96]  M. A. Tejada,et al.  Tetrodotoxin (TTX) as a Therapeutic Agent for Pain , 2012, Marine drugs.

[97]  C. Woolf What is this thing called pain? , 2010, The Journal of clinical investigation.

[98]  Y. Sugimoto,et al.  Prostaglandin receptors: advances in the study of EP3 receptor signaling. , 2002, Journal of biochemistry.

[99]  C. Woolf,et al.  Periganglionic inflammation elicits a distally radiating pain hypersensitivity by promoting COX-2 induction in the dorsal root ganglion , 2009, Pain.

[100]  P. Isakson,et al.  The Acute Antihyperalgesic Action of Nonsteroidal, Anti-Inflammatory Drugs and Release of Spinal Prostaglandin E2 Is Mediated by the Inhibition of Constitutive Spinal Cyclooxygenase-2 (COX-2) but not COX-1 , 2001, The Journal of Neuroscience.

[101]  H. S. Kim,et al.  The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. , 2001, The Journal of clinical investigation.

[102]  T. Grosser,et al.  Role of Prostacyclin in the Cardiovascular Response to Thromboxane A2 , 2002, Science.

[103]  Makoto Murakami,et al.  Reduced Pain Hypersensitivity and Inflammation in Mice Lacking Microsomal Prostaglandin E Synthase-1* , 2004, Journal of Biological Chemistry.

[104]  B. Koller,et al.  Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. , 2001, The Journal of clinical investigation.

[105]  D. Sachs,et al.  The role of PKA and PKCε pathways in prostaglandin E2‐mediated hypernociception , 2009, British journal of pharmacology.

[106]  G. FitzGerald,et al.  Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation. , 2000, The Journal of clinical investigation.

[107]  S. Ferreira Prostaglandins, aspirin-like drugs and analgesia. , 1972, Nature: New biology.

[108]  Garret A FitzGerald,et al.  Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. , 2005, The Journal of clinical investigation.

[109]  E. Mazzon,et al.  Cyclooxygenases 1 and 2 Contribute to Peroxynitrite- Mediated Inflammatory Pain Hypersensitivity , 2022 .

[110]  J. Vane,et al.  Nociception in cyclooxygenase isozyme-deficient mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[111]  J. Falgueyret,et al.  Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX‐2 inhibitor , 1997, British journal of pharmacology.

[112]  D. Benhamou,et al.  The Effect of a Peripheral Block on Inflammation-Induced Prostaglandin E2 and Cyclooxygenase Expression in Rats , 2009, Anesthesia and analgesia.

[113]  Garret A. FitzGerald,et al.  Prostaglandins and Inflammation , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[114]  G. FitzGerald,et al.  Predominance of cyclooxygenase 1 over cyclooxygenase 2 in the generation of proinflammatory prostaglandins in autoantibody-driven K/BxN serum-transfer arthritis. , 2008, Arthritis and rheumatism.

[115]  H. Schaible,et al.  Effects of prostaglandin D2 on tetrodotoxin-resistant Na+ currents in DRG neurons of adult rat , 2011, PAIN.

[116]  I. Chessell,et al.  The Voltage-Gated Sodium Channel Nav1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity , 2006, The Journal of Neuroscience.

[117]  W. Feniuk,et al.  Characterization of the prostanoid receptor types involved in mediating calcitonin gene‐related peptide release from cultured rat trigeminal neurones , 2001, British journal of pharmacology.

[118]  L. Crofford,et al.  Potential roles of microsomal prostaglandin E synthase-1 in rheumatoid arthritis. , 2011, Inflammation and regeneration.

[119]  H. Schaible,et al.  Different effects of spinally applied prostaglandin D2 on responses of dorsal horn neurons with knee input in normal rats and in rats with acute knee inflammation , 2008, Neuroscience.

[120]  Yasuyoshi Watanabe,et al.  Prostaglandin E2 stimulates glutamate release from synaptosomes of rat spinal cord , 1995, Neuroscience Letters.

[121]  H. Schaible,et al.  Changes in the Effect of Spinal Prostaglandin E 2 during Inflammation : Prostaglandin E ( EP 1 – EP 4 ) Receptors in Spinal Nociceptive Processing of Input from the Normal or Inflamed Knee Joint , 2004 .

[122]  S. Narumiya,et al.  Major roles of prostanoid receptors IP and EP(3) in endotoxin-induced enhancement of pain perception. , 2001, Biochemical pharmacology.

[123]  C. Woolf,et al.  Bradykinin Enhances AMPA and NMDA Receptor Activity in Spinal Cord Dorsal Horn Neurons by Activating Multiple Kinases to Produce Pain Hypersensitivity , 2008, The Journal of Neuroscience.

[124]  E. Puré,et al.  Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis , 2006, Proceedings of the National Academy of Sciences.

[125]  H. Schaible,et al.  The intraspinal release of prostaglandin E2 in a model of acute arthritis is accompanied by an up-regulation of cyclo-oxygenase-2 in the spinal cord , 1999, Neuroscience.

[126]  L. Huang,et al.  A critical role of the cAMP sensor Epac in switching protein kinase signalling in prostaglandin E2‐induced potentiation of P2X3 receptor currents in inflamed rats , 2007, The Journal of physiology.

[127]  S. Narumiya,et al.  Contribution of peripheral versus central EP1 prostaglandin receptors to inflammatory pain , 2011, Neuroscience Letters.

[128]  S. Bevan,et al.  PGE2 modulates the tetrodotoxin‐resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP‐protein kinase A cascade. , 1996, The Journal of physiology.

[129]  G. Nicol,et al.  Cyclic AMP mediates the prostaglandin E2-induced potentiation of bradykinin excitation in rat sensory neurons , 1995, Neuroscience.

[130]  A. Hashimoto,et al.  Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase. , 2003, Arthritis and rheumatism.