Premium
Inflammatory pain in peripheral tissue depends on the activation of the TNF‐α type 1 receptor in the primary afferent neuron
Author(s) -
Magalhães Silviane F.,
Manzo Luis P.,
Faria Felipe M.,
OliveiraFusaro Maria C.,
Nishijima Catarine M.,
Vieira Willians F.,
Bonet Ivan J. M.,
Santos Gilson G.,
Tambeli Claudia H.,
Parada Carlos A.
Publication year - 2021
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14985
Subject(s) - hyperalgesia , tumor necrosis factor alpha , nociceptor , pharmacology , medicine , inflammation , receptor , chemistry , endocrinology , nociception
The mechanism underlying the role of tumor necrosis factor alpha (TNF‐α) in the development of inflammatory hyperalgesia has been extensively studied, mainly the role of TNF‐α in the release of pro‐inflammatory cytokines. The current concept relies in the fact that TNF‐α stimulates the cascade release of other pro‐inflammatory cytokines, such as IL‐1β, 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‐α synthesis by thalidomide prevents hyperalgesia without interrupting the synthesis of IL‐1β, IL‐6, and CINC‐1. Therefore, we hypothesized that activation of TNF‐α receptor type 1 (TNFR1) by TNF‐α 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‐α 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‐α 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.