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Motor cortex stimulation and descending antinociception: analysis of periaqueductal gray neurocircuitry

Grant number: 10/13748-5
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2011
Effective date (End): February 28, 2013
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Rosana de Lima Pagano
Grantee:Patrícia Sanae de Souza Lopes
Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
Associated research grant:09/50772-4 - Parkinson disease and pain: mechanisms involved in the nociceptive neuroplasticity and in the effect of motor cortex stimulation in rats, AP.JP


Motor cortex stimulation has been widely used on clinical medicine as a tool to control unresponsive persistent pain, resistant to conventional treatments. However the mechanisms involved in such antinociceptive effect are still remains unclear. Data obtained by our group demonstrated that transdural electrical stimulation of the motor cortex (MCS) inhibits nociceptive response in rats, by acting on opioid system. Furthermore, we found that MCS inhibits GABAergic neurons in the lateral and dorsolateral midbrain periaqueductal grey (PAG), and at the same time, activates ventrolateral PAG neurons. Disinhibition of descending antinociceptive pathway depends on the inhibition of GABAergic interneurons in the PAG, via opioids, cannabinoids, substance P and glutamate. Considering that, the aim of this work is to evaluate PAG neurocircuitry involved on the increase of the nociceptive threshold after MCS. For this purpose, it will be investigated the neuronal activation (Egr-1), concomitantly with the immunostaining for GABA or mu opioid, type 1 cannabinoid, NR1 NMDA and neurokinin 1 receptors in the PAG from animals exposed or not to MCS. This analysis will be characterized by immunohistochemistry and quantified by ELISA in slices. Data obtained herein will help to elucidate the understanding the role of motor cortex in the inhibition of painful response and lead to a better enlightenment of the neurocircuitry of the PAG involved in the antinociception induced by cortical stimulation. Despite the motivational clinical results, some patients are still not beneficed by this neuromodulatory therapy; thus, a better understanding of this effect may contribute to improve the clinical treatments used on pain persistent conditions. (AU)

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Scientific publications
(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)
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, . (09/50772-4, 10/13748-5)

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