Monoaminergic regulation of nociceptive circuitry in a Parkinson's disease rat model

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art_CAMPOS_Monoaminergic_regulation_of_nociceptive_circuitry_in_a_Parkinsons_2019.PDF (3.17 MB)
Citações na Scopus
20
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ACADEMIC PRESS INC ELSEVIER SCIENCE
Autores
CAMPOS, Ana Carolina Pinheiro
BERZUINO, Miria Benatti
HERNANDES, Marina Sorrentino
PAGANO, Rosana Lima
Citação
EXPERIMENTAL NEUROLOGY, v.318, p.12-21, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Pain is a common nonmotor symptom of Parkinson's disease (PD) that remains neglected and misunderstood. Elucidating the nondopaminergic circuitry may be key to better understanding PD and improving current treatments. We investigated the role of monoamines in nociceptive behavior and descending analgesic circuitry in a rat 6-hydroxydopamine (6-OHDA)-induced PD model and explored the resulting motor dysfunctions and inflammatory responses. Rats pretreated with noradrenaline and serotonin reuptake inhibitors were given unilateral striatal 6-OHDA injections and evaluated for mechanical hyperalgesia and motor impairments. Through immunohistochemistry, the number and activation of neurons, and the staining for astrocytes, microglia and enkephalin were evaluated in specific brain structures and the dorsal horn of the spinal cord. The PD model induced bilateral mechanical hyperalgesia that was prevented by reuptake inhibitors in the paw contralateral to the lesion. Reuptake inhibitors also prevented postural immobility and asymmetric rotational behavior in PD rats without interfering with dopaminergic neuron loss or glial activation in the substantia nigra. However, the inhibitors changed the periaqueductal gray circuitry, protected against neuronal impairment in the locus coeruleus and nucleus raphe magnus, and normalized spinal enkephalin and glial staining in lesioned rats. These data indicate that the preservation of noradrenergic and serotonergic systems regulates motor responses and nociceptive circuitry during PD not by interfering directly with nigral lesions but by modulating the opioid system and glial response in the spinal cord. Taken together, these results suggest that nondopaminergic circuitry is essential to the motor and nonmotor symptoms of PD and must be further investigated.
Palavras-chave
Descending analgesia, Noradrenaline, Pain, Parkinson's disease, Serotonin
URI
https://observatorio.fm.usp.br/handle/OPI/33112
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MNE
Artigos e Materiais de Revistas Científicas - HC/IPq
Artigos e Materiais de Revistas Científicas - LIM/45