Involvement of nuclear factor kappa B in the maintenance of persistent inflammatory hypernociception

Author(s):Show less -

Souza, Guilherme R. ^[1] ; Cunha, Thiago M. ^[1] ; Silva, Range L. ^[1] ; Lotufo, Celina M. ^[2] ; Verri, Jr., Waldiceu A. ^[3] ; Funez, Mani I. ^[1] ; Villarreal, Christiane F. ^[1] ; Talbot, Jhimmy ^[1] ; Sousa, Lirlandia P. ^[4] ; Parada, Carlos A. ^[1] ; Cunha, Fernando Q. ^[1] ; Ferreira, Sergio H. ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Uberlandia, Inst Ciencias Biomed, BR-38405320 Uberlandia, MG - Brazil

^[3] Univ Estadual Londrina, Dept Ciencias Patol, Londrina, Parana - Brazil

^[4] Univ Fed Minas Gerais, Fac Farm, Dept Anal Clin & Toxicol, Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: Pharmacology Biochemistry and Behavior; v. 134, p. 49-56, JUL 2015.
• Web of Science Citations: 7

Abstract

The pathophysiology of chronic inflammatory pain remains poorly understood. In this context, we developed an experimental model in which successive daily injection of prostaglandin E-2 (PGE(2)) for 14 days into rat hind paws produces a persistent state of hypernociception (i.e. decrease in mechanical nociceptive threshold). This state persists for more than 30 days after discontinuing PGE(2) injection. In the present study, we investigated the participation of nuclear factor kappa B (NF-kappa B), in the maintenance of this process. Mechanical hypernociception was evaluated using the electronic von Frey test. Activation of NF-kappa B signaling was measured through the determination of NF-kappa B p65 subunit translocation to the nucleus of dorsal root ganglion neurons (DRG) by immunofluorescence and western blotting. Herein, we detected an increase in NF-kappa B p65 subunit translocation to the nucleus of DRG neurons along with persistent inflammatory hypemociception compared with controls. Intrathecal treatment with either dexamethasone or PDTC (NF-kappa B activation inhibitor) after ending of the induction phase of the persistent inflammatory hypernociception, curtailed the hypernociception period as well as reducing NF-kappa B p65 subunit translocation. Treatment with antisense oligonucleotides against the NF-kappa B p65 subunit for 5 consecutive days also reduced persistent inflammatory hypernociception. Inhibition of PKA and PKC epsilon reduced persistent inflammatory hypemociception, which was associated with inhibition of NF-kappa B p65 subunit translocation. Together these results suggest that peripheral activation of NF-kappa B by PKA and PKC in primary sensory neurons plays an important role in maintaining persistent inflammatory pain. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Projects - Thematic Grants