Transcriptional Profiling of TGF-ß Superfamily Members in Lumbar DRGs of Rats Following Sciatic Nerve Axotomy and Activin C Inhibits Neuropathic Pain.
Endocr Metab Immune Disord Drug Targets
; 23(3): 375-388, 2023.
Article
em En
| MEDLINE
| ID: mdl-36201267
ABSTRACT
BACKGROUND:
Neuroinflammation and cytokines play critical roles in neuropathic pain and axon degeneration/regeneration. Cytokines of transforming growth factor-ß superfamily have implications in pain and injured nerve repair processing. However, the transcriptional profiles of the transforming growth factor-ß superfamily members in dorsal root ganglia under neuropathic pain and axon degeneration/regeneration conditions remain elusive.OBJECTIVE:
We aimed to plot the transcriptional profiles of transforming growth factor-ß superfamily components in lumbar dorsal root ganglia of sciatic nerve-axotomized rats and to further verify the profiles by testing the analgesic effect of activin C, a representative cytokine, on neuropathic pain.METHODS:
Adult male rats were axotomized in sciatic nerves, and lumbar dorsal root ganglia were isolated for total RNA extraction or section. A custom microarray was developed and employed to plot the gene expression profiles of transforming growth factor-ß superfamily components. Realtime RT-PCR was used to confirm changes in the expression of activin/inhibin family genes, and then in situ hybridization was performed to determine the cellular locations of inhibin α, activin ßC, BMP-5 and GDF-9 mRNAs. The rat spared nerve injury model was performed, and a pain test was employed to determine the effect of activin C on neuropathic pain.RESULTS:
The expression of transforming growth factor-ß superfamily cytokines and their signaling, including some receptors and signaling adaptors, were robustly upregulated. Activin ßC subunit mRNAs were expressed in the small-diameter dorsal root ganglion neurons and upregulated after axotomy. Single intrathecal injection of activin C inhibited neuropathic pain in spared nerve injury model.CONCLUSION:
This is the first report to investigate the transcriptional profiles of members of transforming growth factor-ß superfamily in axotomized dorsal root ganglia. The distinct cytokine profiles observed here might provide clues toward further study of the role of transforming growth factor-ß superfamily in the pathogenesis of neuropathic pain and axon degeneration/regeneration after peripheral nerve injury.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
/
Neuralgia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Endocr Metab Immune Disord Drug Targets
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
ENDOCRINOLOGIA
/
METABOLISMO
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China