The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses

Cherubino Di Lorenzo, Giorgio Di Lorenzo, Andrea Daverio, Patrizio Pasqualetti, Gianluca Coppola, Ioannis Giannoudas, Gaetano S. Grieco, Cinzia Niolu, Esterina Pascale, Filippo M. Santorelli, Ferdinando Nicoletti, Francesco Pierelli, Alberto Siracusano, Stefano Seri

Research output: Contribution to journalArticle

Abstract

Cortical pain processing is associated with large-scale changes in neuronal connectivity, resulting from neural plasticity phenomena of which brain-derived neurotrophic factor (BDNF) is a central driver. The common single nucleotide polymorphism Val66Met is associated with reduced BDNF activity. Using the trigeminal pain-related evoked potential (tPREP) to repeated electrical painful stimuli, we investigated whether the methionine substitution at codon 66 of the BDNF gene was associated with changes in cortical processing of noxious stimuli. Fifty healthy volunteers were genotyped: 30 were Val/Val and 20 were Met-carriers. tPREPs to 30 stimuli of the right supraorbital nerve using a concentric electrode were recorded. The N2 and P2 component latencies and the N2-P2 amplitude were measured over the 30 stimuli and separately, by dividing the measurements in 3 consecutive blocks of 10 stimuli. The average response to the 30 stimuli did not differ in latency or amplitude between the 2 genotypes. There was a decrease in the N2-P2 amplitude between first and third block in the Val/Val group but not in Met-carriers. BDNF Val66Met is associated with reduced decremental response to repeated electrical stimuli, possibly as a result of ineffective mechanisms of synaptic memory and brain plasticity associated with the polymorphism. PERSPECTIVE: BDNF Val66Met polymorphism affects the tPREP N2-P2 amplitude decrement and influences cortical pain processing through neurotrophin-induced neural plasticity, or through a direct BDNF neurotransmitter-like effect. Our findings suggest that upcoming BDNF central agonists might in the future play a role in pain management.
LanguageEnglish
Pages866-873
Number of pages8
JournalJournal of Pain
Volume13
Issue number9
Early online date21 Aug 2012
DOIs
Publication statusPublished - Sep 2012

Fingerprint

Brain-Derived Neurotrophic Factor
Pain
Genes
Neuronal Plasticity
Evoked Potentials
Nerve Growth Factors
Pain Management
Codon
Methionine
Single Nucleotide Polymorphism
Neurotransmitter Agents
Healthy Volunteers
Electrodes
Genotype
Brain

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Journal of pain. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Di Lorenzo, C, Di Lorenzo, G, Daverio, A, Pasqualetti, P, Coppola, G, Giannoudas, I, Grieco, GS, Niolu, C, Pascale, E, Santorelli, FM, Nicoletti, F, Pierelli, F, Siracusano, A & Seri, S, 'The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses' Journal of pain, vol. 13, no. 9 (2012) DOI http://dx.doi.org/10.1016/j.jpain.2012.05.014

Keywords

  • BDNF
  • Val66Met
  • single nucleotide polymorphism
  • pain-related evoked potential
  • neural plasticity

Cite this

Di Lorenzo, C., Di Lorenzo, G., Daverio, A., Pasqualetti, P., Coppola, G., Giannoudas, I., ... Seri, S. (2012). The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses. Journal of Pain, 13(9), 866-873. https://doi.org/10.1016/j.jpain.2012.05.014
Di Lorenzo, Cherubino ; Di Lorenzo, Giorgio ; Daverio, Andrea ; Pasqualetti, Patrizio ; Coppola, Gianluca ; Giannoudas, Ioannis ; Grieco, Gaetano S. ; Niolu, Cinzia ; Pascale, Esterina ; Santorelli, Filippo M. ; Nicoletti, Ferdinando ; Pierelli, Francesco ; Siracusano, Alberto ; Seri, Stefano. / The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses. In: Journal of Pain. 2012 ; Vol. 13, No. 9. pp. 866-873.
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Di Lorenzo, C, Di Lorenzo, G, Daverio, A, Pasqualetti, P, Coppola, G, Giannoudas, I, Grieco, GS, Niolu, C, Pascale, E, Santorelli, FM, Nicoletti, F, Pierelli, F, Siracusano, A & Seri, S 2012, 'The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses' Journal of Pain, vol. 13, no. 9, pp. 866-873. https://doi.org/10.1016/j.jpain.2012.05.014

The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses. / Di Lorenzo, Cherubino; Di Lorenzo, Giorgio; Daverio, Andrea; Pasqualetti, Patrizio; Coppola, Gianluca; Giannoudas, Ioannis; Grieco, Gaetano S.; Niolu, Cinzia; Pascale, Esterina; Santorelli, Filippo M.; Nicoletti, Ferdinando; Pierelli, Francesco; Siracusano, Alberto; Seri, Stefano.

In: Journal of Pain, Vol. 13, No. 9, 09.2012, p. 866-873.

Research output: Contribution to journalArticle

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T1 - The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses

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AU - Di Lorenzo, Giorgio

AU - Daverio, Andrea

AU - Pasqualetti, Patrizio

AU - Coppola, Gianluca

AU - Giannoudas, Ioannis

AU - Grieco, Gaetano S.

AU - Niolu, Cinzia

AU - Pascale, Esterina

AU - Santorelli, Filippo M.

AU - Nicoletti, Ferdinando

AU - Pierelli, Francesco

AU - Siracusano, Alberto

AU - Seri, Stefano

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AB - Cortical pain processing is associated with large-scale changes in neuronal connectivity, resulting from neural plasticity phenomena of which brain-derived neurotrophic factor (BDNF) is a central driver. The common single nucleotide polymorphism Val66Met is associated with reduced BDNF activity. Using the trigeminal pain-related evoked potential (tPREP) to repeated electrical painful stimuli, we investigated whether the methionine substitution at codon 66 of the BDNF gene was associated with changes in cortical processing of noxious stimuli. Fifty healthy volunteers were genotyped: 30 were Val/Val and 20 were Met-carriers. tPREPs to 30 stimuli of the right supraorbital nerve using a concentric electrode were recorded. The N2 and P2 component latencies and the N2-P2 amplitude were measured over the 30 stimuli and separately, by dividing the measurements in 3 consecutive blocks of 10 stimuli. The average response to the 30 stimuli did not differ in latency or amplitude between the 2 genotypes. There was a decrease in the N2-P2 amplitude between first and third block in the Val/Val group but not in Met-carriers. BDNF Val66Met is associated with reduced decremental response to repeated electrical stimuli, possibly as a result of ineffective mechanisms of synaptic memory and brain plasticity associated with the polymorphism. PERSPECTIVE: BDNF Val66Met polymorphism affects the tPREP N2-P2 amplitude decrement and influences cortical pain processing through neurotrophin-induced neural plasticity, or through a direct BDNF neurotransmitter-like effect. Our findings suggest that upcoming BDNF central agonists might in the future play a role in pain management.

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Di Lorenzo C, Di Lorenzo G, Daverio A, Pasqualetti P, Coppola G, Giannoudas I et al. The Val66Met polymorphism of the BDNF gene influences trigeminal Pain-Related evoked responses. Journal of Pain. 2012 Sep;13(9):866-873. https://doi.org/10.1016/j.jpain.2012.05.014