title: Peripheral inflammatory hyperalgesia depends on the COX increase in the dorsal root ganglion.
abstract: It is well established that dorsal root ganglion (DRG) cells synthesize prostaglandin. However, the role that prostaglandin plays in the inflammatory hyperalgesia of peripheral tissue has not been established. Recently, we have successfully established a technique to inject drugs (3 μL) directly into the L5-DRG of rats, allowing in vivo identification of the role that DRG cell-derived COX-1 and COX-2 play in the development of inflammatory hyperalgesia of peripheral tissue. IL-1β (0.5 pg) or carrageenan (100 ng) was administered in the L5-peripheral field of rat hindpaw and mechanical hyperalgesia was evaluated after 3 h. Administration of a nonselective COX inhibitor (indomethacin), selective COX-1 (valeryl salicylate), or selective COX-2 (SC-236) inhibitors into the L5-DRG prevented the hyperalgesia induced by IL-1β. Similarly, oligodeoxynucleotide-antisense against COX-1 or COX-2, but not oligodeoxynucleotide-mismatch, decreased their respective expressions in the L5-DRG and prevented the hyperalgesia induced by IL-1β in the hindpaw. Immunofluorescence analysis demonstrated that the amount of COX-1 and COX-2, constitutively expressed in TRPV-1(+) cells of the DRG, significantly increased after carrageenan or IL-1β administration. In addition, indomethacin administered into the L5-DRG prevented the increase of PKCε expression in DRG membrane cells induced by carrageenan. Finally, the administration of EP1/EP2 (7.5 ng) or EP4 (10 µg) receptor antagonists into L5-DRG prevented the hyperalgesia induced by IL-1β in the hindpaw. In conclusion, the results of this study suggest that the inflammatory hyperalgesia in peripheral tissue depends on activation of COX-1 and COX-2 in C-fibers, which contribute to the induction and maintenance of sensitization of primary sensory neurons.
authors: Department of Structural and Functional Biology, Institute of Biology,  State University of Campinas, Campinas, 13083-862, São Paulo,  Brazil.
authors: Dionéia
authors: D
authors: Araldi
authors: Luiz Fernando
authors: LF
authors: Ferrari
authors: Celina Monteiro
authors: CM
authors: Lotufo
authors: André Schwambach
authors: AS
authors: Vieira
authors: Maria Carolina Pedro
authors: MC
authors: Athié
authors: Jozi Godoy
authors: JG
authors: Figueiredo
authors: Djane Braz
authors: DB
authors: Duarte
authors: Claudia Herrera
authors: CH
authors: Tambeli
authors: Sérgio Henrique
authors: SH
authors: Ferreira
authors: Carlos Amilcar
authors: CA
authors: Parada
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006930:Hyperalgesia / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D053583:Interleukin-1beta / Q000494:pharmacology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D053583:Interleukin-1beta; D008565:Membrane Proteins; D018078:Receptors, Prostaglandin E; D050916:TRPV Cation Channels; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D051744:Protein Kinase C-epsilon; D007213:Indomethacin
references: Neuron. 1999 Sep;24(1):253-60
references: 10677042
references: Physiol Behav. 1976 Dec;17(6):1031-6
references: 14677603
references: Neuroreport. 1997 Mar 24;8(5):1249-51
references: 9175123
references: PLoS One. 2011 Mar 04;6(3):e17360
references: 21394197
references: Braz J Med Biol Res. 2004 Mar;37(3):391-9
references: 15060709
references: Inflamm Res. 1998 Dec;47(12):482-7
references: 9892042
references: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19038-43
references: 18799742
references: Br J Pharmacol. 1997 Dec;122(8):1593-604
references: 9422803
references: Pain. 2009 Jan;141(1-2):127-34
references: 19081189
references: Neuroscience. 1999;93(2):775-81
references: 10465460
references: Pain. 2009 Mar;142(1-2):59-67
references: 19135800
references: Eur J Neurosci. 2000 Mar;12(3):911-20
references: 10762321
references: Cancer Invest. 1998;16(7):509-27
references: 9774958
references: Acta Neuropathol. 1993;86(6):636-44
references: 7508671
references: Pain. 2002 Jan;95(1-2):143-52
references: 11790477
references: J Neurochem. 1999 Nov;73(5):2206-13
references: 10537081
references: Br J Pharmacol. 2009 Mar;156(5):826-34
references: 19220288
references: Pain. 1994 May;57(2):217-223
references: 7916452
references: J Neurosci. 2001 Aug 15;21(16):5847-53
references: 11487607
references: Anesthesiology. 2002 Jul;97(1):170-6
references: 12131119
references: Pharmacol Rev. 1994 Jun;46(2):205-29
references: 7938166
references: Inflamm Res. 1996 Oct;45(10):499-502
references: 8912014
references: Anal Biochem. 2010 Jun 15;401(2):318-20
references: 20206115
references: J Neurosci Methods. 2007 Jan 30;159(2):236-43
references: 16973217
references: J Neurochem. 2009 Sep;110(5):1557-66
references: 19573019
references: J Neuroimmunol. 1998 Aug 14;89(1-2):26-34
references: 9726822
references: Hippocampus. 2002;12(4):457-64
references: 12201630
references: Nat New Biol. 1971 Jun 23;231(25):235-7
references: 5284361
references: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2923-8
references: 12589028
references: Anat Rec. 1977 May;188(1):45-7
references: 869231
references: Eur J Pharmacol. 1980 Oct 17;67(2-3):313-6
references: 6893963
references: Pol J Pharmacol Pharm. 1978 Mar-Jun;30(2-3):133-40
references: 673924
references: Neuroscience. 2001;105(4):971-85
references: 11530235
references: J Pharmacol Exp Ther. 1998 Jun;285(3):1031-8
references: 9618405
references: Nat New Biol. 1971 Jun 23;231(25):232-5
references: 5284360
references: Br J Pharmacol. 2003 Apr;138(7):1351-7
references: 12711636
references: J Pharmacol Toxicol Methods. 1994 Dec;32(4):197-200
references: 7881133