Parkinson disease and pain: mechanisms involved in the nociceptive neuroplasticity and in the effect of motor cortex stimulation in rats

• Grant number: 09/50772-4
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: June 01, 2010 - May 31, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosana de Lima Pagano
• Grantee: Rosana de Lima Pagano
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
• Associated scholarship(s): 10/13748-5 - Motor cortex stimulation and descending antinociception: analysis of periaqueductal gray neurocircuitry, BP.MS

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of nigrostriatal dopamine neurons, resulting in extrapiramidal motor control alterations. Most part of DP patients relates pain, sometimes previously to motor and cognitives disorders, typical symptoms of disease. Experimentally, the reduction of nociceptive threshold in parkinsonian rats in different models of nociception was observed, however the mechanisms involved still remain unclear. The aim of this project is to investigate the nociceptive neuroplasticity in rats submited to PD model by unilateral striatal 6-hydroxydoparnine, evaluating the activation pattem of nervous cells and the mediators involved with the nociceptive pathway. The nociceptive response will be investigated in models of thermical and mechanical nociception. The neuronal and microglial activation will be determinated by c-Fos and OX-42 immunolabel, respectively. Also, the response of the neurons in the dorsal hom of spinal cord (DHSC) will be evaluated, using in vivo electrophysiology. The expression of tyrosine hydroxylase, dopamine-p-decarboxylase, tryptophan-hydroxylase, GAD 65/67, GABA, enkephalin, DI and D2 dopamine and u, k and opioid receptors will be deterrninated, by immunohistochemistry and immunoblotting. The evaluated areas will be DHSC, medial and lateral ventral posterior nuclei of the thalamus, periaqueductal grey, locus ceruleus, raphe magno nucleus, substantia nigra and striate. Once that motor cortex electrical stimulation (MCS) is used in the therapy of patients with advanced PD, the MCS effect on hemiparkinsonian rats will be investigated, evaluating the parameters previously described and the behavioural response in the rotational test and open field. This study could contribute with the understanding of nociceptive neuroplasticity that occur during PD and also to facilite the comprehension of modulatory role of motor cortex in this pathology, providing tools for the improvement of techniques used during this and other central nervous system alterations. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DIMOV, LUIZ FABIO; FRANCIOSI, ADRIANO CARDOZO; PINHEIRO CAMPOS, ANA CAROLINA; BRUNONI, ANDRE RUSSOWSKY; PAGANO, ROSANA LIMA. Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats. PLoS One, v. 11, n. 4, APR 12 2016. (12/20911-5, 09/50772-4)

PINHEIRO CAMPOS, ANA CAROLINA; BERZUINO, MIRIA BENATTI; HERNANDES, MARINA SORRENTINO; FONOFF, ERICH TALAMONI; PAGANO, ROSANA LIMA. Monoaminergic regulation of nociceptive circuitry in a Parkinson's disease rat model. Experimental Neurology, v. 318, p. 12-21, AUG 2019. (09/50772-4, 14/20209-4)

SOUZA LOPES, PATRICIA SANAE; PINHEIRO CAMPOS, ANA CAROLINA; FONOFF, ERICH TALAMONI; GIORGETTI BRITTO, LUIZ ROBERTO; PAGANO, ROSANA LIMA. Motor cortex and pain control: exploring the descending relay analgesic pathways and spinal nociceptive neurons in healthy conscious rats. Behavioral and Brain Functions, v. 15, MAR 25 2019. (09/50772-4, 10/13748-5)

CAMPOS, ANA CAROLINA P.; BERZUINO, MIRIA B.; BARBOSA, GABRIELA R.; FREIRE, HELENA M. R. C.; LOPES, PATRICIA S.; ASSIS, DANIELLE V.; FONOFF, ERICH T.; PAGANO, ROSANA L.. Motor Cortex Stimulation Reversed Hypernociception, Increased Serotonin in Raphe Neurons, and Caused Inhibition of Spinal Astrocytes in a Parkinson's Disease Rat Model. CELLS, v. 10, n. 5, MAY 2021. (14/20209-4, 09/50772-4)

SILVA, GUILHERME D.; LOPES, PATRICIA S. S.; FONOFF, ERICH T.; PAGANO, ROSANA L.. The spinal anti-inflammatory mechanism of motor cortex stimulation: cause of success and refractoriness in neuropathic pain?. JOURNAL OF NEUROINFLAMMATION, v. 12, JAN 20 2015. (09/50772-4, 12/11925-2)