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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inflammatory pain in peripheral tissue depends on the activation of the TNF-alpha type 1 receptor in the primary afferent neuron

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Author(s):
de Magalhaes, Silviane F. [1] ; Manzo, Luis P. [1] ; de Faria, Felipe M. [1] ; de Oliveira-Fusaro, Maria C. [2] ; Nishijima, Catarine M. [1] ; Vieira, Willians F. [1] ; Bonet, Ivan J. M. [1] ; dos Santos, Gilson G. [1] ; Tambeli, Claudia H. [1] ; Parada, Carlos A. [1]
Total Authors: 10
Affiliation:
[1] State Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas - Brazil
[2] State Univ Campinas UNICAMP, Sch Appl Sci, Limeira - Brazil
Total Affiliations: 2
Document type: Journal article
Source: European Journal of Neuroscience; v. 53, n. 2, p. 376-389, JAN 2021.
Web of Science Citations: 0
Abstract

The mechanism underlying the role of tumor necrosis factor alpha (TNF-alpha) in the development of inflammatory hyperalgesia has been extensively studied, mainly the role of TNF-alpha in the release of pro-inflammatory cytokines. The current concept relies in the fact that TNF-alpha stimulates the cascade release of other pro-inflammatory cytokines, such as IL-1 beta, IL-6, and IL-8 (CINC-1 in rats), triggering the release of the final inflammatory mediator prostaglandin E-2(PGE(2)) and sympathetic amines that directly sensitize the nociceptors. However, this may not be the sole mechanism involved as the blockade of TNF-alpha synthesis by thalidomide prevents hyperalgesia without interrupting the synthesis of IL-1 beta, IL-6, and CINC-1. Therefore, we hypothesized that activation of TNF-alpha receptor type 1 (TNFR1) by TNF-alpha increases nociceptors' susceptibility to the action of PGE(2)and dopamine. We have found out that intrathecal administration of oligodeoxynucleotide-antisense (ODN-AS) against TNFR1 or thalidomide prevented carrageenan-induced hyperalgesia. The co-administration of TNF-alpha with a subthreshold dose of PGE(2)or dopamine that does not induce hyperalgesia by itself in the hind paw of Wistar rats pretreated with dexamethasone (to prevent the endogenous release of cytokines) induced a robust hyperalgesia that was prevented by intrathecal treatment with ODN-AS against TNFR1. We consider that the activation of neuronal TNFR1 by TNF-alpha decisively increases the susceptibility of the peripheral afferent neuron to the action of final inflammatory mediators - PGE(2)and dopamine - that ultimately induce hyperalgesia. This mechanism may also underlie the analgesic action of thalidomide. (AU)

FAPESP's process: 14/25153-7 - Analysis of differential gene expression of dorsal ganglion root cell in a model of diabetes and peripheral diabetic neuropathy
Grantee:Carlos Amilcar Parada
Support Opportunities: Regular Research Grants
FAPESP's process: 17/23485-0 - Interaction between neurons and satellite cells in dorsal root ganglia: ATP signaling to the development of inflammatory and neuropathic hyperalgesia.
Grantee:Carlos Amilcar Parada
Support Opportunities: Regular Research Grants