Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury.
BACKGROUND
The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide in neuropathic pain has yet to be investigated.


RESULTS
Prolonged upregulation of VGF mRNA and protein was observed in injured dorsal root ganglion neurons, central terminals and their target dorsal horn neurons. Intrathecal application of TLQP-62, the C-terminal active portion of VGF (5-50 nmol) to naïve rats caused a long-lasting mechanical and cold behavioral allodynia. Direct actions of 50 nM TLQP-62 upon dorsal horn neuron excitability was demonstrated in whole cell patch recordings in spinal cord slices and in receptive field analysis in intact, anesthetized rats where significant actions of VGF were upon spontaneous activity and cold evoked responses.


CONCLUSIONS
VGF expression is therefore highly modulated in nociceptive pathways following peripheral nerve injury and can cause dorsal horn cell excitation and behavioral hypersensitivity in naïve animals. Together the results point to a novel and powerful role for VGF in neuropathic pain.
Moss
Andrew
A
UCL Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK. Andrew.Moss@pfizer.com
Ingram
Rachel
R
Koch
Stephanie
S
Theodorou
Andria
A
Low
Lucie
L
Baccei
Mark
M
Hathway
Gareth J
GJ
Costigan
Michael
M
Salton
Stephen R
SR
Fitzgerald
Maria
M
D000818:Animals; D003080:Cold Temperature; D005727:Ganglia, Spinal / Q000378:metabolism; D008954:Models, Biological; D009437:Neuralgia / Q000150:complications / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D015854:Up-Regulation
D009479:Neuropeptides; D012333:RNA, Messenger; C522413:VGF peptide