The Val66Met polymorphism of the BDNF gene influences trigeminal pain-related evoked responses.
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.


CONCLUSIONS
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.
Don Carlo Gnocchi Onlus Foundation, Milan, Italy. cherub@inwind.it
Cherubino
C
Di Lorenzo
Giorgio
G
Di Lorenzo
Andrea
A
Daverio
Patrizio
P
Pasqualetti
Gianluca
G
Coppola
Ioannis
I
Giannoudas
Ylenia
Y
Barone
Gaetano S
GS
Grieco
Cinzia
C
Niolu
Esterina
E
Pascale
Filippo M
FM
Santorelli
Ferdinando
F
Nicoletti
Francesco
F
Pierelli
Alberto
A
Siracusano
Stefano
S
Seri
D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography; D005071:Evoked Potentials / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D010146:Pain / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012737:Sex Factors; D014276:Trigeminal Nerve / Q000503:physiopathology; D014633:Valine / Q000235:genetics*; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine