Peripheral inflammatory hyperalgesia depends on the COX increase in the dorsal root ganglion

Dionéia Araldi; Luiz Fernando Ferrari; Celina Monteiro Lotufo; André Schwambach Vieira; Maria Carolina Pedro Athié; Jozi Godoy Figueiredo; Djane Braz Duarte; Claudia Herrera Tambeli; Sérgio Henrique Ferreira; Carlos Amilcar Parada

doi:10.1073/pnas.1220668110

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Peripheral inflammatory hyperalgesia depends on the COX increase in the dorsal root ganglion

Journal article

Peer reviewed

Peripheral inflammatory hyperalgesia depends on the COX increase in the dorsal root ganglion

Dionéia Araldi, Luiz Fernando Ferrari, Celina Monteiro Lotufo, André Schwambach Vieira, Maria Carolina Pedro Athié, Jozi Godoy Figueiredo, Djane Braz Duarte, Claudia Herrera Tambeli, Sérgio Henrique Ferreira and Carlos Amilcar Parada

Proceedings of the National Academy of Sciences - PNAS, Vol.110(9), pp.3603-3608

02/26/2013

DOI: 10.1073/pnas.1220668110

PMID: 23401543

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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.

Biological Sciences

Pharmacology

Details

Title: Subtitle: Peripheral inflammatory hyperalgesia depends on the COX increase in the dorsal root ganglion
Creators: Dionéia Araldi - Universidade Estadual de Campinas (UNICAMP)
Luiz Fernando Ferrari - Universidade de São Paulo
Celina Monteiro Lotufo - Universidade de São Paulo
André Schwambach Vieira - Universidade Estadual de Campinas (UNICAMP)
Maria Carolina Pedro Athié - Universidade Estadual de Campinas (UNICAMP)
Jozi Godoy Figueiredo - Universidade de São Paulo
Djane Braz Duarte - Universidade de São Paulo
Claudia Herrera Tambeli - Universidade Estadual de Campinas (UNICAMP)
Sérgio Henrique Ferreira - Universidade de São Paulo
Carlos Amilcar Parada - Universidade Estadual de Campinas (UNICAMP)
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.110(9), pp.3603-3608
DOI: 10.1073/pnas.1220668110
PMID: 23401543
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Number of pages: 6
Alternative title: COX activation in DRG and peripheral hyperalgesia
Language: English
Date published: 02/26/2013
Academic Unit: Neuroscience and Pharmacology
Record Identifier: 9985178664602771

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