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Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia
BACKGROUND: 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. AIMS: We investigated...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055187/ https://www.ncbi.nlm.nih.gov/pubmed/24944866 http://dx.doi.org/10.1002/brb3.214 |
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author | Dieb, Wisam Ouachikh, Omar Durif, Franck Hafidi, Aziz |
author_facet | Dieb, Wisam Ouachikh, Omar Durif, Franck Hafidi, Aziz |
author_sort | Dieb, Wisam |
collection | PubMed |
description | BACKGROUND: 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. AIMS: 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. RESULTS AND DISCUSSION: 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. |
format | Online Article Text |
id | pubmed-4055187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-40551872014-06-18 Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia Dieb, Wisam Ouachikh, Omar Durif, Franck Hafidi, Aziz Brain Behav Original Research BACKGROUND: 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. AIMS: 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. RESULTS AND DISCUSSION: 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. BlackWell Publishing Ltd 2014-05 2014-02-20 /pmc/articles/PMC4055187/ /pubmed/24944866 http://dx.doi.org/10.1002/brb3.214 Text en © 2014 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Dieb, Wisam Ouachikh, Omar Durif, Franck Hafidi, Aziz Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia |
title | Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia |
title_full | Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia |
title_fullStr | Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia |
title_full_unstemmed | Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia |
title_short | Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia |
title_sort | lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055187/ https://www.ncbi.nlm.nih.gov/pubmed/24944866 http://dx.doi.org/10.1002/brb3.214 |
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