Electrical stimulation of the posterior insula induces mechanical analgesia in a rodent model of neuropathic pain by modulating GABAergic signaling and activity in the pain circuitry

Author(s):Show less -

Alonso-Matielo, Heloisa ^[1] ; Goncalves, Elizamara S. ^[1] ; Campos, Mariana ^[1] ; Oliveira, Victoria R. S. ^[1] ; Toniolo, Elaine F. ^[2] ; Alves, Adilson S. ^[3] ; Lebrun, Ivo ^[4] ; de Andrade, Daniel C. ^{[5, 6]} ; Teixeira, Manoel J. ^[5] ; Britto, Luiz R. G. ^[3] ; Hamani, Clement ^[7] ; Dale, Camila S. ^{[1, 8]}

Affiliation

^[1] Univ Sao Paulo, Dept Anat, Inst Biomed Sci, Av Prof Lineu 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 Tatuape, BR-03071000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508000 Sao Paulo, SP - Brazil

^[4] Inst Butantan, Lab Biochem & Biophys, Sao Paulo - Brazil

^[5] Cent Inst, Dept Neurol, Av Dr Eneas Carvalho Aguiar 255, 5th Floor, Room 50, BR-05403900 Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Inst Canc Octavio Friers Oliveira, Sao Paulo - Brazil

^[7] Univ Toronto, Harquail Ctr Neuromodulat, Sunnybrook Res Inst, Toronto, ON M4N 3M5 - Canada

^[8] Univ Sao Paulo, Med Sch, Dept Surg Tech, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Brain Research; v. 1754, MAR 1 2021.
• Web of Science Citations: 0

Abstract

The insula has emerged as a critical target for electrical stimulation since it influences pathological pain states. We investigated the effects of repetitive electrical stimulation of the insular cortex (ESI) on mechanical nociception, and general locomotor activity in rats subjected to chronic constriction injury (CCI) of the sciatic nerve. We also studied neuroplastic changes in central pain areas and the involvement of GABAergic signaling on ESI effects. CCI rats had electrodes implanted in the left agranular posterior insular cortex (pIC), and mechanical sensitivity was evaluated before and after one or five daily consecutive ESIs (15 min each, 60 Hz, 210 mu s, 1 V). Five ESIs (repetitive ESI) induced sustained mechanical antinociception from the first to the last behavioral assessment without interfering with locomotor activity. A marked increase in Fos immunoreactivity in pIC and a decrease in the anterior and mid-cingulate cortex, periaqueductal gray and hippocampus were noticed after five ESIs. The intrathecal administration of the GABA(A) receptor antagonist bicuculline methiodide reversed the stimulation-induced antinociception after five ESIs. ESI increased GAD65 levels in pIC but did not interfere with GABA, glutamate or glycine levels. No changes in GFAP immunoreactivity were found in this work. Altogether, the results indicate the efficacy of repetitive ESI for the treatment of experimental neuropathic pain and suggest a potential influence of pIC in regulating pain pathways partially through modulating GABAergic signaling. (AU)

• FAPESP's process: 17/25399-4 - Study of GABAergic modulation in the circuitry involved in analgesia induced by the electrical stimulation of the insular cortex
• Grantee: Heloísa Alonso Matielo
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/17136-8 - Study of the molecular mechanisms involved in the low level laser therapy-induced antinociception in experimental diabetic neuropathy
• Grantee: Camila Squarzoni Dale
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/18483-1 - Photobiomodulation as complementary therapy in the treatment of diabetic wounds: effects on exteroceptive pain sensitivity, healing process and possible molecular mechanisms
• Grantee: Victória Regina da Silva Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/07411-7 - Involvement of the opioid system in the analgesia induced by the electrical stimulation of the insular cortex
• Grantee: Elizamara Santos Gonçalves
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• 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