Antinociceptive effects of IL-6R vs. glucocorticoid receptors during rat hind paw inflammatory pain.
Neurosci Lett
; 738: 135356, 2020 11 01.
Article
en En
| MEDLINE
| ID: mdl-32898615
ABSTRACT
BACKGROUND:
The glucocorticoid receptor (GR) plays a role in inflammatory pain modulation. However, the specific role played by interleukin 6 receptor (IL-6R) in these processes remains elusive. The present study aimed to investigate the extent of inflammation induced by IL-6R and GR.METHODS:
Male Wistar rats were treated with Freund's complete adjuvant to induce right hind paw inflammation. The levels of IL-6Rα and GR were evaluated in the spinal cord and dorsal root ganglion using Western blot and immunofluorescence assays. Subsequently, we examined the nociceptive behavioral changes following the binding of IL-6R with a GR agonist and/or antagonist, as well as the concentration levels of IL-6 and soluble IL-6R (sIL-6R) in the serum and cerebrospinal fluid. Moreover, the spinal levels of IL-6, IL-6Rα, gp130, JAK2, pJAK2, STAT3, pSTAT3, c-fos, GFAP, and Iba-1 were assessed following anti-IL-6R antibody, sgp130, and dexamethasone intrathecal administration.RESULTS:
Right hind paw inflammation resulted in significant upregulation of IL-6Rα expression in spinal nociceptive neurons, astrocytes, and microglia cells, as well as increased of IL-6Rα and GR colocalization. Notably, anti-IL-6R or dexamethasone attenuated the nociceptive behavior in a dose-dependent manner. Isobologram analysis indicated the sub-additive effects with a concomitant decrease in the spinal levels of IL-6, pJAK2, pSTAT3, c-fos, GFAP, and Iba-1 and increase in the sIL-6R level.CONCLUSION:
The enhanced mechanical sensitivity accompanying the increase of IL-6Rα and GR was attenuated by anti-IL-6R and dexamethasone application, and the sub-additive effects were regulated by the decreased activation of neurons and glial cells and modulated by IL-6/JAK2/STAT3 signaling pathway, which might be attributed to IL-6 induced trans-signaling.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dolor
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Receptores de Glucocorticoides
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Receptores de Interleucina-6
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Inflamación
Límite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Año:
2020
Tipo del documento:
Article