Brazilian Journal of Pain
https://brjp.org.br/article/doi/10.5935/2595-0118.20220049-en
Brazilian Journal of Pain
Original Article

Electrical stimulation of the posterior insular cortex induces opioid and cannabinoid-dependent antinociception and regulates glial cells in the spinal cord

A estimulação elétrica do córtex insular posterior induz antinocicepção opioide e canabinoide dependente e regula células da glia na medula espinal

Elizamara Santos Gonçalves; Heloísa Alonso Matielo; Manoel Jacobsen Teixeira; Daniel Ciampi de Andrade; Clement Hamani; Camila Squarzoni Dale

http://dx.doi.org/10.5935/2595-0118.20220049-en BrJP, vol.5, n3, p.239-247, 2022
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Abstract

BACKGROUND AND OBJECTIVES: Half of neuropathic pain patients still end up failing clinical treatments. Electrical stimulation of the posterior insular cortex (ESI) modulates sensory and nociceptive circuits. This study evaluated the effects of a range of frequencies of ESI proposed to improve neuropathic pain.

METHODS: Male Sprague Dawley rats, 280-340 g, submitted to the chronic constriction of the right sciatic nerve were tested for mechanical sensitivity using the paw pressure and von Frey flaments tests, and for thermal sensitivity using the hot plate test. The rats were submitted to ESI 10, 60 or 100 Hz (one, five or seven ESI, 15 min, 210 µs, 1V), applied to the posterior insular cortex, and were evaluated in the tests before and after ESI, or in follow-up of 48, 72 and 168h. The open field evaluated general activity after ESI 5. The involvment of opioid and cannabinoid testes were evaluated through treatment with naloxone and SR1416A - antagonist and inverse agonist/antagonist of the receptors, respectively, after ESI 5, while activation of astrocytes, marked by glial fibrillary acid protein (GFAP), and of microglia, marked by IBA-1 (glial marker), in the spinal cord evaluated by immunohistochemistry.

RESULTS: Data demonstrate that 10, 60, and 100 Hz ESIs modulate mechanical and thermal sensitivity. ESI 5 increased immunoreactivity of GFAP in the spinal cord, without altering IBA-1 (glial marker). Naloxone and SR141716A reversed the antinociception of 60 Hz ESI 5. 60 Hz ESI 7 induced antinociception up to 72h.

CONCLUSION: 60 Hz ESI induces opioid and cannabinoid-dependent antinociception and regulates glia.

HIGHLIGHTS

  • 60 Hz-delivered ESI was the best analgesic protocol for the insular stimulation.
  • Data showed a prolonged analgesic effect up to 72h after repetitive ESI.
  • ESI regulates glia activation in pain modulatory system.

Keywords

Chronic pain, Electric stimulation, Neuroglia

Resumo

JUSTIFICATIVA E OBJETIVOS: Metade dos pacientes com dor neuropática são refratários aos tratamentos. A estimulação elétrica do córtex insular (EECI) posterior modula circuitos sensoriais e nociceptivos. Assim, este estudo avaliou os efeitos de uma faixa de frequências de EECI como tratamento em modelo animal de dor neuropática.

MÉTODOS: Ratos machos, Sprague Dawley, 280-340 g, submetidos a cirurgia para indução de constrição crônica (ICC) do nervo isquiático direito, foram avaliados em relação à sensibilidade mecânica com a utilização do teste de pressão de pata e de flamentos de von Frey, e sensibilidade térmica usando o teste de placa quente. Os ratos foram submetidos a EECI de 10, 60 ou 100 Hz (uma, cinco ou sete EECI, 15 min, 210 µs, 1V), aplicada ao córtex insular posterior esquerdo, e avaliados nos testes antes e após EECI, ou em follow up de 48, 72 e 168 horas. Por meio do teste de campo aberto, avaliou-se a atividade geral após a EECI5. O envolvimento de receptores opioides e canabinoides foi avaliado por meio da administração de naloxona e SR141716A - antagonista e agonista/antagonista inverso dos receptores, respectivamente - após a EECI 5, enquanto a ativação de astrócitos - marcada por proteína ácida fibrilar glial (GFAP), e de micróglia - marcada por IBA-1 - na medula espinal foi avaliada por imuno-histoquímica.

RESULTADOS: Os dados mostraram que EECI em 10, 60 e 100 Hz modulam a sensibilidade mecânica e térmica dos animais. A EECI 5 aumentou a imunorreatividade de GFAP na medula espinhal, sem alterar IBA-1 (marcador glial). Naloxona e SR141716A reverteram a antinocicepção produzida por EECI 5 de 60 Hz. EECI 7 de 60 Hz induziu antinocicepção por até 72 horas.

CONCLUSÃO: A EECI 60 Hz produz antinocicepção dependente de opioides e canabinoides e regula a glia.

DESTAQUES

  • A EECI de 60 Hz foi o melhor protocolo analgésico para nossa estimulação insular.
  • Os dados mostram um efeito analgésico prolongado de até 72h após repetidas EECI.
  • A EECI regula a ativação da glia no sistema modulatório da dor.

Palavras-chave

Dor crônica, Estimulação elétrica, Neuroglia

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Submitted date:
07/14/2022

Accepted date:
09/13/2022

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