Neuron type-specific effects of brain-derived neurotrophic factor in rat superficial dorsal horn and their relevance to 'central sensitization'.
J Physiol
; 584(Pt 2): 543-63, 2007 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-17761774
ABSTRACT
Chronic constriction injury (CCI) of the rat sciatic nerve increases the excitability of the spinal dorsal horn. This 'central sensitization' leads to pain behaviours analogous to human neuropathic pain. We have established that CCI increases excitatory synaptic drive to putative excitatory, 'delay' firing neurons in the substantia gelatinosa but attenuates that to putative inhibitory, 'tonic' firing neurons. Here, we use a defined-medium organotypic culture (DMOTC) system to investigate the long-term actions of brain-derived neurotrophic factor (BDNF) as a possible instigator of these changes. The age of the cultures and their 5-6 day exposure to BDNF paralleled the protocol used for CCI in vivo. Effects of BDNF (200 ng ml(-1)) in DMOTC were reminiscent of those seen with CCI in vivo. These included decreased synaptic drive to 'tonic' neurons and increased synaptic drive to 'delay' neurons with only small effects on their membrane excitability. Actions of BDNF on 'delay' neurons were exclusively presynaptic and involved increased mEPSC frequency and amplitude without changes in the function of postsynaptic AMPA receptors. By contrast, BDNF exerted both pre- and postsynaptic actions on 'tonic' cells; mEPSC frequency and amplitude were decreased and the decay time constant reduced by 35%. These selective and differential actions of BDNF on excitatory and inhibitory neurons contributed to a global increase in dorsal horn network excitability as assessed by the amplitude of depolarization-induced increases in intracellular Ca(2+). Such changes and their underlying cellular mechanisms are likely to contribute to CCI-induced 'central sensitization' and hence to the onset of neuropathic pain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Medula Espinal
/
Fator Neurotrófico Derivado do Encéfalo
/
Células do Corno Posterior
/
Neuropatia Ciática
/
Neuralgia
Limite:
Animals
Idioma:
En
Revista:
J Physiol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Canadá
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM