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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The spinal anti-inflammatory mechanism of motor cortex stimulation: cause of success and refractoriness in neuropathic pain?

Texto completo
Autor(es):
Silva, Guilherme D. [1] ; Lopes, Patricia S. S. [1] ; Fonoff, Erich T. [1, 2] ; Pagano, Rosana L. [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Hosp Sirio Libanes, Lab Neuromodulat & Expt Pain, BR-01308060 Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, Dept Neurol, Div Funct Neurosurg, BR-01060970 Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF NEUROINFLAMMATION; v. 12, JAN 20 2015.
Citações Web of Science: 14
Resumo

Background: Motor cortex stimulation (MCS) is an effective treatment in neuropathic pain refractory to pharmacological management. However, analgesia is not satisfactorily obtained in one third of patients. Given the importance of understanding the mechanisms to overcome therapeutic limitations, we addressed the question: what mechanisms can explain both MCS effectiveness and refractoriness? Considering the crucial role of spinal neuroimmune activation in neuropathic pain pathophysiology, we hypothesized that modulation of spinal astrocyte and microglia activity is one of the mechanisms of action of MCS. Methods: Rats with peripheral neuropathy (chronic nerve injury model) underwent MCS and were evaluated with a nociceptive test. Following the test, these animals were divided into two groups: MCS-responsive and MCS-refractory. We also evaluated a group of neuropathic rats not stimulated and a group of sham-operated rats. Some assays included rats with peripheral neuropathy that were treated with AM251 (a cannabinoid antagonist/inverse agonist) or saline before MCS. Finally, we performed immunohistochemical analyses of glial cells (microglia and astrocytes), cytokines (TNF-alpha and IL-1 beta), cannabinoid type 2 (CB2), mu-opioid (MOR), and purinergic P2X4 receptors in the dorsal horn of the spinal cord (DHSC). Findings: MCS reversed mechanical hyperalgesia, inhibited astrocyte and microglial activity, decreased proinflammatory cytokine staining, enhanced CB2 staining, and downregulated P2X4 receptors in the DHSC ipsilateral to sciatic injury. Spinal MOR staining was also inhibited upon MCS. Pre-treatment with AM251 blocked the effects of MCS, including the inhibitory mechanism on cells. Finally, MCS-refractory animals showed similar CB2, but higher P2X4 and MOR staining intensity in the DHSC in comparison to MCS-responsive rats. Conclusions: These results indicate that MCS induces analgesia through a spinal anti-neuroinflammatory effect and the activation of the cannabinoid and opioid systems via descending inhibitory pathways. As a possible explanation for MCS refractoriness, we propose that CB2 activation is compromised, leading to cannabinoid resistance and consequently to the perpetuation of neuroinflammation and opioid inefficacy. (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
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 12/11925-2 - Modulação das células da glia espinhais durante a reversão da dor neuropática induzida por estimulação cortical
Beneficiário:Guilherme Diogo Silva
Linha de fomento: Bolsas no Brasil - Iniciação Científica