Parkinson's disease and pain: Modulation of nociceptive circuitry in a rat model of nigrostriatal lesion

Autor(es)

Domenici, Roberta A. ^[1] ; Campos, Aria Carolina P. ^[1] ; Maciel, Soraya T. ^[1] ; Berzuino, Miria B. ^[1] ; Hernandes, Marina S. ^[2] ; Fonoff, Erich T. ^{[1, 3]} ; Pagano, Rosana L. ^[1]

Afiliação do(s) autor(es)

^[1] Hosp Sirio Libanes, Lab 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, Sch Med, Dept Neurol, Div Funct Neurosurg, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Neurology; v. 315, p. 72-81, MAY 2019.
• Citações Web of Science: 3

Resumo

Parkinson's disease (PD) is a neurodegenerative disorder that causes progressive dysfunction of dopaminergic and non-dopaminergic neurons, generating motor and nonmotor signs and symptoms. Pain is reported as the most bothersome nonmotor symptom in PD; however, pain remains overlooked and poorly understood. In this study, we evaluated the nociceptive behavior and the descending analgesia circuitry in a rat model of PD. Three independent experiments were performed to investigate: i) thermal nociceptive behavior; ii) mechanical nociceptive behavior and dopaminergic repositioning; and iii) modulation of the pain control circuitry. The rat model of PD, induced by unilateral striatal 6-hydroxydopamine (6-OHDA), did not interfere with thermal nociceptive responses; however, the mechanical nociceptive threshold was decreased bilaterally compared to that of naive or striatal saline-injected rats. This response was reversed by apomorphine or levodopa treatment. Striatal 6-OHDA induced motor impairments and reduced dopaminergic neuron immunolabeling as well as the pattern of neuronal activation (c-Fos) in the substantia nigra ipsilateral (IPL) to the lesion. In the midbrain periaqueductal gray (PAG), 6-OHDA-induced lesion increased IPL and decreased contralateral PAG GABAergic labeling compared to control. In the dorsal horn of the spinal cord, lesioned rats showed bilateral inhibition of enkephalin and p-opioid receptor labeling. Taken together, we demonstrated that the unilateral 6-OHDA-induced PD model induces bilateral mechanical hypernociception, which is reversed by dopamine restoration, changes in the PAG circuitry, and inhibition of spinal opioidergic regulation, probably due to impaired descending analgesic control. A better understanding of pain mechanisms in PD patients is critical for developing better therapeutic strategies to improve their quality of life. (AU)

• 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: 10/11653-7 - Estudo da neuroplasticidade nociceptiva no modelo de doença de Parkinson em ratos
• Beneficiário: Soraya Takahashi Maciel
• 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