Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model.
Scand J Pain
; 16: 1-9, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28850381
ABSTRACT
BACKGROUND AND AIMS:
Despite widespread use, the efficacy of neuraxial glucocorticoids for neuropathic pain is subject to debate. Since most glucocorticoid actions are mediated through its receptor, we explored the effects of intrathecal methylprednisolone acetate (MPA) on total glucocorticoid receptor (tGR) levels and activation of the glucocorticoid receptor (phosphorylated state=pGR) within the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) in a spinal nerve ligation (SNL) model in rats.METHODS:
Rats received unilateral ligation of the L5/L6 spinal nerves and were treated with two intrathecal doses of either 400µg MPA or 0.9% saline with a 72-h interval. Plantar tactile thresholds were measured over time. Seven days after drug treatment, DRG and SDH were harvested to assess tGR and pGR levels using immunohistochemistry and qPCR.RESULTS:
Allodynia, defined by lowered tactile withdrawal thresholds after SNL, was unaltered by intrathecal MPA. In saline controls, mRNA levels of tGR did not change after SNL in the DRGs or SDH. tGR and pGR protein levels in the SDH however, significantly increased on the ipsilateral side of SNL compared to the contralateral side and to naïve tissue. When treating rats with MPA, tGR mRNA levels were significantly reduced in the SDH compared to saline controls. tGR and pGR protein levels, however were not significantly lower compared to saline controls.CONCLUSIONS:
In intrathecal MPA treated rats, tGR mRNA levels decreased after SNL. However this did not result in lower tGR and pGR protein levels compared to saline controls, and did not decrease ligation-induced mechanical hypersensitivity. IMPLICATIONS Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Nervos Espinhais
/
Injeções Espinhais
/
Receptores de Glucocorticoides
/
Acetato de Metilprednisolona
/
Glucocorticoides
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Scand J Pain
Ano de publicação:
2017
Tipo de documento:
Article