Spinal P2X4 Receptors Involved in Visceral Hypersensitivity of Neonatal Maternal Separation Rats.
Purinergic Signal
; 19(1): 113-122, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-35648361
ABSTRACT
Recent studies have demonstrated the vital role of P2X4 receptors (a family of ATP-gated non-selective cation channels) in the transmission of neuropathic and inflammatory pain. In this study, we investigated the role of spinal P2X4 receptors in chronic functional visceral hypersensitivity of neonatal maternal separation (NMS) rats. A rat model of irritable bowel syndrome was established by neonatal maternal separation. Visceral sensitivity was assessed by recording the response of the external oblique abdominal muscle to colorectal distension. P2X4 receptor antagonist and agonist were administrated intrathecally. The expression of P2X4 receptor was examined by Western Blot and immunofluorescence. The effect of P2X4 receptor antagonist on expression of brain-derived neurotrophic factor (BDNF) was assessed by Western Blot. We found neonatal maternal separation enhanced visceral hypersensitivity and increased the expression of P2X4 receptor in spinal thoracolumbar and lumbosacral segments of rats. Pharmacological results showed that visceral sensitivity was attenuated after intrathecal injection of P2X4 receptor antagonist, 5-BDBD, at doses of 10 nM or 100 nM, while visceral sensitivity was enhanced after intrathecal injection of P2X4 receptor agonist C5-TDS at doses of 10 µM or 15 µM. In addition, the spinal expression of BDNF significantly increased in NMS rats and intrathecal injection of 5-BDBD significantly decreased the expression of BDNF especially in NMS rats. C5-TDS failed to increase EMG amplitude in the presence of ANA-12 in control rats. Our results suggested the spinal P2X4 receptors played an important role in visceral hypersensitivity of NMS rats through BDNF.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome do Intestino Irritável
/
Dor Visceral
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Purinergic Signal
Ano de publicação:
2023
Tipo de documento:
Article