Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia
Identifieur interne : 000072 ( Main/Exploration ); précédent : 000071; suivant : 000073Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia
Auteurs : Wisam Dieb [France] ; Omar Ouachikh [France] ; Franck Durif [France] ; Aziz Hafidi [France]Source :
- Brain and Behavior [ 2162-3279 ] ; 2014.
Abstract
Pain constitutes the major non motor syndrome in Parkinson's disease (PD) and includes neuropathic pain; however current drug therapies used to alleviate it have only limited efficacy. This is probably due to poor understanding of the mechanisms underlying it.
We investigated a major class of trigeminal neuropathic pain, dynamic mechanical allodynia (DMA), in a rat model of PD and in which a bilateral 6-hydroxy dopamine (6-OHDA) injection was administered to produce a lesion of the nigrostriatal dopaminergic pathway.
Lesioned animals presented significant DMA in the orofacial area that occurred from 4 days to 5 weeks post-injury. To investigate a segmental implication in the neuropathic pain induced by dopamine depletion, the expression of the isoform gamma of the protein kinase C (PKCg) and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) was explored in the medullary dorsal horn (MDH). There was a high increase in PKCg expression in the III and IIi laminae of the MDH of lesioned-animals compared to shams. pERK1/2 expression was also significantly high in the ipsilateral MDH of lesioned rats in response to non-noxious tactile stimulus of the orofacial region. Since pERK1/2 is expressed only in response to nociceptive stimuli in the dorsal spinal horn, the current study demonstrates that non-noxious stimuli evoke allodynic response. Intraperitoneal and intracisternal administrations of bromocriptine, a dopamine 2 receptor (D2R) agonist, significantly decreased DMA compared to control rats injected with saline. These data demonstrate for the first time that nigrostriatal dopaminergic depletion produces trigeminal neuropathic pain that at least involves a segmental mechanism. In addition, bromocriptine was shown to have a remarkable analgesic effect on this neuropathic pain symptom.
Url:
DOI: 10.1002/brb3.214
PubMed: 24944866
PubMed Central: 4055187
Affiliations:
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type="wicri:Area/Main/Exploration">000072</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia</title><author><name sortKey="Dieb, Wisam" sort="Dieb, Wisam" uniqKey="Dieb W" first="Wisam" last="Dieb">Wisam Dieb</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne</institution><addr-line>Clermont-Ferrand, EA7280, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Clermont-Ferrand, EA7280</wicri:regionArea><wicri:noRegion>EA7280</wicri:noRegion><wicri:noRegion>EA7280</wicri:noRegion></affiliation></author><author><name sortKey="Ouachikh, Omar" sort="Ouachikh, Omar" uniqKey="Ouachikh O" first="Omar" last="Ouachikh">Omar Ouachikh</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne</institution><addr-line>Clermont-Ferrand, EA7280, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Clermont-Ferrand, EA7280</wicri:regionArea><wicri:noRegion>EA7280</wicri:noRegion><wicri:noRegion>EA7280</wicri:noRegion></affiliation></author><author><name sortKey="Durif, Franck" sort="Durif, Franck" uniqKey="Durif F" first="Franck" last="Durif">Franck Durif</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne</institution><addr-line>Clermont-Ferrand, EA7280, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Clermont-Ferrand, 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xml:lang="fr">France</country><wicri:regionArea>Clermont-Ferrand, EA7280</wicri:regionArea><wicri:noRegion>EA7280</wicri:noRegion><wicri:noRegion>EA7280</wicri:noRegion></affiliation></author></analytic><series><title level="j">Brain and Behavior</title><idno type="ISSN">2162-3279</idno><idno type="e-ISSN">2162-3279</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Pain constitutes the major non motor syndrome in Parkinson's disease (PD) and includes neuropathic pain; however current drug therapies used to alleviate it have only limited efficacy. This is probably due to poor understanding of the mechanisms underlying it.</p></sec><sec><title>Aims</title><p>We investigated a major class of trigeminal neuropathic pain, dynamic mechanical allodynia (DMA), in a rat model of PD and in which a bilateral 6-hydroxy dopamine (6-OHDA) injection was administered to produce a lesion of the nigrostriatal dopaminergic pathway.</p></sec><sec><title>Results and discussion</title><p>Lesioned animals presented significant DMA in the orofacial area that occurred from 4 days to 5 weeks post-injury. To investigate a segmental implication in the neuropathic pain induced by dopamine depletion, the expression of the isoform gamma of the protein kinase C (PKCg) and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) was explored in the medullary dorsal horn (MDH). There was a high increase in PKCg expression in the III and IIi laminae of the MDH of lesioned-animals compared to shams. pERK1/2 expression was also significantly high in the ipsilateral MDH of lesioned rats in response to non-noxious tactile stimulus of the orofacial region. Since pERK1/2 is expressed only in response to nociceptive stimuli in the dorsal spinal horn, the current study demonstrates that non-noxious stimuli evoke allodynic response. Intraperitoneal and intracisternal administrations of bromocriptine, a dopamine 2 receptor (D2R) agonist, significantly decreased DMA compared to control rats injected with saline. These data demonstrate for the first time that nigrostriatal dopaminergic depletion produces trigeminal neuropathic pain that at least involves a segmental mechanism. In addition, bromocriptine was shown to have a remarkable analgesic effect on this neuropathic pain symptom.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Altier, N" uniqKey="Altier N">N Altier</name></author><author><name sortKey="Stewart, J" uniqKey="Stewart J">J Stewart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alvarez, P" uniqKey="Alvarez P">P Alvarez</name></author><author><name sortKey="Dieb, W" uniqKey="Dieb W">W Dieb</name></author><author><name sortKey="Hafidi, A" uniqKey="Hafidi A">A Hafidi</name></author><author><name sortKey="Voisin, Dl" uniqKey="Voisin D">DL Voisin</name></author><author><name sortKey="Dallel, R" uniqKey="Dallel R">R Dallel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ansah, Ob" uniqKey="Ansah O">OB Ansah</name></author><author><name sortKey="Leite Almeida, H" uniqKey="Leite Almeida H">H 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Wasner</name></author><author><name sortKey="Deuschl, G" uniqKey="Deuschl G">G Deuschl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wood, Pb" uniqKey="Wood P">PB Wood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woolf, Cj" uniqKey="Woolf C">CJ Woolf</name></author><author><name sortKey="Mannion, Rj" uniqKey="Mannion R">RJ Mannion</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zengin Toktas, Y" uniqKey="Zengin Toktas Y">Y Zengin-Toktas</name></author><author><name sortKey="Authier, N" uniqKey="Authier N">N Authier</name></author><author><name sortKey="Denizot, H" uniqKey="Denizot H">H Denizot</name></author><author><name sortKey="Chassain, C" uniqKey="Chassain C">C Chassain</name></author><author><name sortKey="Hafidi, A" uniqKey="Hafidi A">A Hafidi</name></author><author><name sortKey="Llorca, Pm" uniqKey="Llorca P">PM Llorca</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li></country><region><li>Auvergne</li><li>Auvergne-Rhône-Alpes</li></region></list><tree><country name="France"><noRegion><name sortKey="Dieb, Wisam" sort="Dieb, Wisam" uniqKey="Dieb W" first="Wisam" last="Dieb">Wisam Dieb</name></noRegion><name sortKey="Durif, Franck" sort="Durif, Franck" uniqKey="Durif F" first="Franck" last="Durif">Franck Durif</name><name sortKey="Durif, Franck" sort="Durif, Franck" uniqKey="Durif F" first="Franck" last="Durif">Franck Durif</name><name sortKey="Hafidi, Aziz" sort="Hafidi, Aziz" uniqKey="Hafidi A" first="Aziz" last="Hafidi">Aziz Hafidi</name><name sortKey="Ouachikh, Omar" sort="Ouachikh, Omar" uniqKey="Ouachikh O" first="Omar" last="Ouachikh">Omar Ouachikh</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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