Origins, Actions and Dynamic Expression Patterns of the Neuropeptide VGF in Rat Peripheral and Central Sensory Neurones Following Peripheral Nerve Injury

Abstract

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.

VGF: An inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers

“…In SOD1 G93A transgenic mice, the VGF content in SMI-32 immunopositive spinal motor neurons was reduced in asymptomatic animals (approximately 75 days), and continued to decline as animals weakened (Zhao et al, 2008). A densely immunoreactive sensory projection reaches the superficial laminae of the dorsal horn (Ferri et al, 1992), in which VGF is co-localized with substance P and partly with CGRP, as shown in dorsal root ganglia or their cultures (Moss et al, 2008;Rizzi et al, 2008). However, things are probably more complex, since the expression of VGF mRNA in spinal ganglia is indeed intense in small diameter primary sensory neurons, but by no means absent in larger diameter, neurofilament protein expressing neurons (Ferri et al, 1997).…”

“…Conversely, intrathecal injection of the longer peptide TLQP-62 induced long lasting mechanical and cold allodynia (Moss et al, 2008). Upon axotomy, dorsal root ganglion neurons showed substantial accumulation of VGF peptides, both in culture (Ferri et al, 1997;Riedl et al, 2009), and in vivo (Riedl et al, 2009).…”

Clioquinol Increases the Expression of VGF, a Neuropeptide Precursor, Through Induction of c-Fos Expression

“…A peripheral injection of TLQP-21 (residues 557 to 576 of VGF) was shown to increase the pain-related licking response in a mouse model (24). The intrathecal application of TLQP-62 (C-terminal 62 amino acids of VGF) to naive rats was found to cause long-lasting mechanical and cold behavioral allodynia (25). AQEE-30 and LQEQ-19, corresponding to the last 30 and 19 amino acids of VGF, respectively, were also shown to evoke thermal hyperalgesia in rats (26).…”

The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity

“…VGF and peptides derived from its proteolytic processing have been implicated in the control of energy balance and metabolism as well as in neuroplasticity associated with learning, memory, depression, and chronic pain [9,19,20,22,28,35,43]. …”

“…TLQP-62 [9]), and dorsal horn neurons (i.e. TLQP-62 [28]). Furthermore, intrathecal administration of C-terminal VGF peptides results in thermal hyperalgesia (i.e.…”