HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 584/2/543    most recent jphysiol.2007.141267v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lu, V. B. Articles by Smith, P. A. Search for Related Content PubMed PubMed Citation Articles by Lu, V. B. Articles by Smith, P. A. Related Collections Neuroscience

¹ Department of Pharmacology
² Department of Physiology
³ Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada

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 Ca²⁺. Such changes and their underlying cellular mechanisms are likely to contribute to CCI-induced ‘central sensitization’ and hence to the onset of neuropathic pain.

(Received 25 July 2007; accepted after revision 23 August 2007; first published online 30 August 2007)
Corresponding author P. A. Smith: Department of Pharmacology, University of Alberta, 9.75 Medical Sciences Building, Edmonton, Alberta, Canada, T6G 2H7. Email: peter.a.smith{at}ualberta.ca