Electrical stimulation of the insular cortex as a novel target for the relief of refractory pain: An experimental approach in rodents

Author(s)

Dimov, Luiz Fabio ^[1] ; Toniolo, Elaine Flamia ^{[1, 2]} ; Alonso-Matielo, Heloisa ^[1] ; de Andrade, Daniel Ciampi ^{[3, 4]} ; Garcia-Larrea, Luis ^{[5, 6]} ; Ballester, Gerson ^[2] ; Teixeira, Manoel Jacobsen ^[3] ; Dale, Camila Squarzoni ^{[1, 7]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Ave Prof Linea Prestes 2415, ICB 3, Cidade Univ, BR-05508900 Sao Paulo, SP - Brazil

^[2] Univ Cidade Sao Paulo, Ctr Res Neurosci, R Cesario Galero 448-475, BR-03071000 Sao Paulo, SP - Brazil

^[3] Cent Inst, Dept Neurol, Ave Dr Eneas de Carvalho Aguiar 255, 5th Floor, BR-05403900 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Inst Canc Octavio Frias Oliveira, Sao Paulo - Brazil

^[5] Hosp Civils Lyon, Lyon - France

^[6] Univ Claude Bernard Lyon 1, Inserm U1028, Lyon Ctr Neurosci, Cent Integrat Pain NeuroPain, Lyon - France

^[7] Univ Sao Paulo, Med Sch, Dept Surg Tech, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Behavioural Brain Research; v. 346, p. 86-95, JUL 2 2018.
• Web of Science Citations: 5

Abstract

Cortical electrical stimulation (CES) has shown to be an effective therapeutic alternative for neuropathic pain refractory to pharmacological treatment. The primary motor cortex(M1) was the main cortical target used in the vast majority of both invasive and non-invasive studies. Despite positive results M1-based approaches still fail to relieve pain in a significant proportion of individuals. It has been advocated that the direct stimulation of cortical areas directly implicated in the central integration of pain could increase the efficacy of analgesic brain stimulation. Here, we evaluated the behavioral effects of electrical stimulation of the insular cortex (ESI) on pain sensitivity in an experimental rat model of peripheral neuropathy, and have described the pathways involved. Animals underwent chronic constriction of the sciatic nerve in the right hind limb and had concentric electrodes implanted in the posterior dysranular insular cortex. Mechanical nociception responses were evaluated before and at the end of a 15-min session of ESI (60 Hz, 210 mu s, 1 V). ESI reversed mechanical hypersensitivity in the paw contralateral to the brain hemisphere stimulated, without inducing motor impairment in the open-field test. Pharmacological blockade of mu-opioid (MOR) or type 1-cannabinoid receptors (CB1R) abolished ESI-induced antinociceptive effects. Evaluation of CB1R and MOR spatial expression demonstrated differential modulation of CB1R and MOR in the periaqueductal gray matter (PAG) of ESI-treated rats in sub-areas involved in pain processing/modulation. These results indicate that ESI induces antinociception by functionally modulating opioid and cannabinoid systems in the PAG pain circuitry in rats with experimentally induced neuropathic pain. (AU)

• FAPESP's process: 12/50176-5 - Effect of hemopressin - an inverse agonist of cannabinoid receptors type 1 - in diabetes mellitus-induced neuropathy in mice
• Grantee: Camila Squarzoni Dale
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/23522-8 - Antinociception induced by electrical stimulation of the insular cortex of rats with peripheral neuropathy: screening on thermal sensitivity, general activity and anxiety
• Grantee: Heloísa Alonso Matielo
• Support Opportunities: Scholarships in Brazil - Scientific Initiation