Regulation of increased glutamatergic input to spinal dorsal horn neurons by mGluR5 in diabetic neuropathic pain.
J Neurochem
; 112(1): 162-72, 2010 Jan.
Article
en En
| MEDLINE
| ID: mdl-19840219
ABSTRACT
Diabetic neuropathic pain is associated with increased glutamatergic input in the spinal dorsal horn. Group I metabotropic glutamate receptors (mGluRs) are involved in the control of neuronal excitability, but their role in the regulation of synaptic transmission in diabetic neuropathy remains poorly understood. Here we studied the role of spinal mGluR5 and mGluR1 in controlling glutamatergic input in a rat model of painful diabetic neuropathy induced by streptozotocin. Whole-cell patch-clamp recordings of lamina II neurons were performed in spinal cord slices. The amplitude of excitatory post-synaptic currents (EPSCs) evoked from the dorsal root and the frequency of spontaneous EPSCs (sEPSCs) were significantly higher in diabetic than in control rats. The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) inhibited evoked EPSCs and sEPSCs more in diabetic than in control rats. Also, the percentage of neurons in which sEPSCs and evoked EPSCs were affected by MPEP or the group I mGluR agonist was significantly higher in diabetic than in control rats. However, blocking mGluR1 had no significant effect on evoked EPSCs and sEPSCs in either groups. The mGluR5 protein level in the dorsal root ganglion, but not in the dorsal spinal cord, was significantly increased in diabetic rats compared with that in control rats. Furthermore, intrathecal administration of MPEP significantly increased the nociceptive pressure threshold only in diabetic rats. These findings suggest that increased mGluR5 expression on primary afferent neurons contributes to increased glutamatergic input to spinal dorsal horn neurons and nociceptive transmission in diabetic neuropathic pain.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Glutamato Metabotrópico
/
Ácido Glutámico
/
Células del Asta Posterior
/
Neuropatías Diabéticas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos