Cortical Neurostimulation and N-Methyl- D-Aspartate Glutamatergic Receptor Activation in the Dysgranular Layer of the Posterior Insular Cortex Modulate Chronic Neuropathic Pain

Author(s)

Pereira, Renata Cristina Martins ; Medeiros, Priscila ; Coimbra, Norberto Cysne ; Machado, Helio Rubens ; de Freitas, Renato Leonardo

• Document type: Journal article
• Source: NEUROMODULATION; v. 26, n. 8, p. 15-pg., 2023-12-05.

Abstract

Background and Aims: The dysgranula parts of the posterior insular cortex (PIC) stimulation (PICS) has been investigated as a new putative cortical target for nonpharmacologic therapies in patients with chronic and neuropathic pain (NP). This work investigates the neural bases of insula neurostimulation-induced antinociception and glutamatergic neurochemical mechanisms recruited by the PICS in animals with neuropathy.Materials and Methods: Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve or Sham procedure ("false operated"). Either the Cascade Blue 3000 MW lysine-fixable dextran (CBD) or the biotinylated dextran amine 3000 MW (BDA) neural tract tracer was microinjected into the PIC. The electrical PICS was performed at a low frequency (20 mu A, 100 Hz) for 15 seconds by a deep brain stimulation device. PIC N-methyl-D-aspartate (NMDA) receptors (NMDAR) blockade with the selective antagonist LY235959 (at 2, 4, and 8 nmol/200 nL) followed by PICS was investigated in rats with CCI.Results: PIC sends projections to the caudal pontine reticular nucleus, alpha part of the parvicellular reticular nucleus, dorso -medial tegmental area, and secondary somatosensory cortex (S2). PICS decreased both mechanical and cold allodynia in rats with chronic NP. Blockade of NMDAR in the PIC with LY235959 at 8 nmol attenuated PICS-produced antinociception. (AU)

• FAPESP's process: 09/17258-5 - Study of the involvement of nitrergic system and of glutamatergic and cannabinoid-mediated neurotransmission from the medial prefrontal cortex in the analgesia induced by elaborated escape reactions evoked by GABAergic blockade in the medial hypothalamus
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/25167-2 - Role of glutamatergic, endocannabinoid and endovaniloid systems of medial pre-frontal cortex in neurophatic pain model: Investigation of panic and chronic pain comorbidity
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/07902-2 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 14/11869-0 - Multi-use equipment approved in grant 2013/12916-0: deep brain stimulation (DBS) (Thomas mini matrix system - Thomas recording GmbH® - Winchester Strasse - Giessen - Germany)
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 13/12916-0 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 17/13560-5 - Effect of deep brain stimulation and cannabidiol treatment in the subthalamic nucleus on the motors and non-Motors symptoms in the experimental model of Parkinson Disease
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral