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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Experimental Neurology; v. 318, p. 12-21, AUG 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 09/50772-4 - Parkinson disease and pain: mechanisms involved in the nociceptive neuroplasticity and in the effect of motor cortex stimulation in rats
• Grantee: Rosana de Lima Pagano
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/20209-4 - Involvement of glial cells in descending analgesic pathway in model of nigrostriatal lesion
• Grantee: Ana Carolina Pinheiro Campos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation