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

  • Renata Cristina Martins Pereira
    Affiliations
    Multi-User Center of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Laboratory of Neurosciences of Pain & Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Brain Protection Laboratory in Childhood, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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  • Priscila Medeiros
    Affiliations
    Multi-User Center of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Laboratory of Neurosciences of Pain & Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Department of Neurosciences and Behavioral Sciences. Department of Pharmacology. Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Federal University of São Carlos Pain Clinic, Federal University of São Carlos, São Carlos, São Paulo, Brazil
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  • Norberto Cysne Coimbra
    Affiliations
    Multi-User Center of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Department of Neurosciences and Behavioral Sciences. Department of Pharmacology. Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Behavioural Neurosciences Institute, Ribeirão Preto, São Paulo, Brazil
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  • Hélio Rubens Machado
    Affiliations
    Brain Protection Laboratory in Childhood, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil
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  • Renato Leonardo de Freitas
    Correspondence
    Address correspondence to: Renato Leonardo de Freitas, Lic, BsC, Biology, MSc, DSc, Laboratory of Neurosciences of Pain & Emotions, and Multi-User Center of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Av Bandeirantes, 3900, Ribeirão Preto, São Paulo, Brazil.
    Affiliations
    Multi-User Center of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Laboratory of Neurosciences of Pain & Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Department of Neurosciences and Behavioral Sciences. Department of Pharmacology. Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Behavioural Neurosciences Institute, Ribeirão Preto, São Paulo, Brazil
    Search for articles by this author

      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 μA, 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, dorsomedial 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.

      Conclusion

      Neuroanatomic projections from the PIC to pontine reticular nuclei and S2 may contribute to chronic NP signaling. PICS attenuates the chronic NP, and the NMDA glutamatergic system in the PIC may be involved in PICS-induced antinociception in rodents with NP conditions.

      Graphical abstract

      Keywords

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