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Open Access 01-12-2008 | Research

Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury

Authors: Andrew Moss, Rachel Ingram, Stephanie Koch, Andria Theodorou, Lucie Low, Mark Baccei, Gareth J Hathway, Michael Costigan, Stephen R Salton, Maria Fitzgerald

Published in: Molecular Pain | Issue 1/2008

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.

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.

Conclusion

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.

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Baron R: Mechanisms of disease: neuropathic pain – a clinical perspective. Nat Clin Pract Neurol 2006, 2: 95–106. 10.1038/ncpneuro0113CrossRefPubMed

Kehlet H, Jensen TS, Woolf CJ: Persistent postsurgical pain: risk factors and prevention. Lancet 2006, 367: 1618–1625. 10.1016/S0140-6736(06)68700-XCrossRefPubMed

Thacker MA, Clark AK, Marchand F, McMahon SB: Pathophysiology of peripheral neuropathic pain: immune cells and molecules. Anesth Analg 2007, 105: 838–847. 10.1213/01.ane.0000275190.42912.37CrossRefPubMed

Woolf CJ: Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. Life Sci 2004, 74: 2605–2610. 10.1016/j.lfs.2004.01.003CrossRefPubMed

Salter MW: Cellular signalling pathways of spinal pain neuroplasticity as targets for analgesic development. Curr Top Med Chem 2005, 5: 557–567. 10.2174/1568026054367638CrossRefPubMed

Campbell JN, Meyer RA: Mechanisms of neuropathic pain. Neuron 2006, 52: 77–92. 10.1016/j.neuron.2006.09.021PubMedCentralCrossRefPubMed

Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y: BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005, 438: 1017–1021. 10.1038/nature04223CrossRefPubMed

Yajima Y, Narita M, Usui A, Kaneko C, Miyatake M, Narita M, Yamaguchi T, Tamaki H, Wachi H, Seyama Y, Suzuki T: Direct evidence for the involvement of brain-derived neurotrophic factor in the development of a neuropathic pain-like state in mice. J Neurochem 2005, 93: 584–594. 10.1111/j.1471-4159.2005.03045.xCrossRefPubMed

Lacroix-Fralish ML, Tawfik VL, Tanga FY, Spratt KF, DeLeo JA: Differential spinal cord gene expression in rodent models of radicular and neuropathic pain. Anesthesiology 2006, 104: 1283–1292. 10.1097/00000542-200606000-00025CrossRefPubMed

10.

Pezet S, McMahon SB: Neurotrophins: Mediators and Modulators of Pain. Annu Rev Neurosci 2006, 29: 507–538. 10.1146/annurev.neuro.29.051605.112929CrossRefPubMed

11.

Costigan M, Befort K, Karchewski L, Griffin RS, D'Urso D, Allchorne A, Sitarski J, Mannion JW, Pratt RE, Woolf CJ: Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 2002, 3: 16. 10.1186/1471-2202-3-16PubMedCentralCrossRefPubMed

12.

Griffin RS, Costigan M, Brenner GJ, Ma CH, Scholz J, Moss A, Allchorne AJ, Stahl GL, Woolf CJ: Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. J Neurosci 2007, 27: 8699–708. 10.1523/JNEUROSCI.2018-07.2007CrossRefPubMed

13.

Levi A, Ferri GL, Watson E, Possenti R, Salton SR: Processing, distribution, and function of VGF, a neuronal and endocrine peptide precursor. Cell Mol Neurobiol 2004, 24: 517–533. 10.1023/B:CEMN.0000023627.79947.22CrossRefPubMed

14.

Salton SR: Nucleotide sequence and regulatory studies of VGF, a nervous system-specific mRNA that is rapidly and relatively selectively induced by nerve growth factor. J Neurochem 1991, 57: 991–996. 10.1111/j.1471-4159.1991.tb08248.xCrossRefPubMed

15.

Alder J, Thakker-Varia S, Bangasser DA, Kuroiwa M, Plummer MR, Shors TJ, Black IB: Brain-derived neurotrophic factor-induced gene expression reveals novel actions of VGF in hippocampal synaptic plasticity. J Neurosci 2003, 23: 10800–10808.PubMedCentralPubMed

16.

Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR, Duman RS: Antidepressant actions of the exercise-regulated gene VGF. Nat Med 2007, 13: 1476–1482. 10.1038/nm1669CrossRefPubMed

17.

Decosterd I, Woolf CJ: Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 2000, 87: 149–158. 10.1016/S0304-3959(00)00276-1CrossRefPubMed

18.

Snyder SE, Salton SR: Expression of VGF mRNA in the adult rat central nervous system. J Comp Neurol 1998, 394: 91–105. 10.1002/(SICI)1096-9861(19980427)394:1<91::AID-CNE7>3.0.CO;2-CCrossRefPubMed

19.

Snyder SE, Cheng HW, Murray KD, Isackson PJ, McNeill TH, Salton SR: The messenger RNA encoding VGF, a neuronal peptide precursor, is rapidly regulated in the rat central nervous system by neuronal activity, seizure and lesion. Neuroscience 1998, 82: 7–19. 10.1016/S0306-4522(97)00280-7CrossRefPubMed

20.

Lu VB, Ballanyi K, Colmers WF, Smith PA: Neuron type-specific effects of brain-derived neurotrophic factor in rat superficial dorsal horn and their relevance to 'central sensitization'. J Physiol 2007, 584: 543–563. 10.1113/jphysiol.2007.141267PubMedCentralCrossRefPubMed

21.

Moss A, Blackburn-Munro G, Garry EM, Blakemore JA, Dickinson T, Rosie R, Mitchell R, Fleetwood-Walker SM: A role of the ubiquitin-proteasome system in neuropathic pain. J Neurosci 2002, 22: 1363–1372.PubMed

22.

Bremner LR, Fitzgerald M: Postnatal tuning of cutaneous inhibitory receptive fields in the rat. J Physiol 2008, 586: 1529–1537. 10.1113/jphysiol.2007.145672PubMedCentralCrossRefPubMed

23.

Ingram RA, Fitzgerald M, Baccei ML: Developmental changes in the fidelity and short-term plasticity of GABAergic synapses in the neonatal rat dorsal horn. J Neurophysiol 2008, 99: 3144–3150. 10.1152/jn.01342.2007CrossRefPubMed

Title: Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury
Authors: Andrew Moss
Rachel Ingram
Stephanie Koch
Andria Theodorou
Lucie Low
Mark Baccei
Gareth J Hathway
Michael Costigan
Stephen R Salton
Maria Fitzgerald
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2008
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-4-62

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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