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

Autor(es)

Pinheiro Campos, Ana Carolina ^[1] ; Berzuino, Miria Benatti ^[1] ; Hernandes, Marina Sorrentino ^[2] ; Fonoff, Erich Talamoni ^{[1, 3]} ; Pagano, Rosana Lima ^[1]

Afiliação do(s) autor(es)

^[1] Hosp Sirio Libanes, Div Neurosci, Rua Prof Daher Cutait 69, BR-01308060 Sao Paulo, SP - Brazil

^[2] Emory Univ, Dept Med, Atlanta, GA 30322 - USA

^[3] Univ Sao Paulo, Med Sch, Dept Neurol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Neurology; v. 318, p. 12-21, AUG 2019.
• Citações Web of Science: 0

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. (AU)

• Processo FAPESP: 09/50772-4 - Doença de Parkinson e dor: mecanismos envolvidos na neuroplasticidade nociciptiva e no efeito da estimulação do córtex motor em ratos
• Beneficiário: Rosana de Lima Pagano
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 12/07232-1 - Entendendo a hiperalgesia mecânica induzida pela lesão nigroestriatal: avaliação do padrão de ativação central
• Beneficiário: Miriã Benatti Berzuino
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/20209-4 - Envolvimento das células da glia na via analgésica descendente no modelo de lesão nigroestriatal
• Beneficiário: Ana Carolina Pinheiro Campos
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 12/07231-5 - Envolvimento noradrenérgico e serotonérgico nas alterações nociceptivas e motoras observadas em ratos hemiparkinsonianos
• Beneficiário: Ana Carolina Pinheiro Campos
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica