The role of dorsomedial and ventrolateral columns of the periaqueductal gray matter and in situ 5-HT2A and 5-HT2C serotonergic receptors in post-ictal antinociception

Authors

  • Renato Leonardo de Freitas,

    1. Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (USP), Ribeirão Preto (SP), Brazil
    2. Institute for Neuroscience and Behavior (INeC), Ribeirão Preto (SP), Brazil
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  • Rithiele Cristina de Oliveira,

    1. Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (USP), Ribeirão Preto (SP), Brazil
    2. Institute for Neuroscience and Behavior (INeC), Ribeirão Preto (SP), Brazil
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  • Ricardo de Oliveira,

    1. Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (USP), Ribeirão Preto (SP), Brazil
    2. Institute for Neuroscience and Behavior (INeC), Ribeirão Preto (SP), Brazil
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  • Tatiana Paschoalin-Maurin,

    1. Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (USP), Ribeirão Preto (SP), Brazil
    2. Institute for Neuroscience and Behavior (INeC), Ribeirão Preto (SP), Brazil
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  • Fernando Morgan de Aguiar Corrêa,

    1. Laboratory of Central Control of the Arterial Pressure, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (USP), Ribeirão Preto (SP), Brazil
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  • Norberto Cysne Coimbra

    Corresponding author
    1. Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (USP), Ribeirão Preto (SP), Brazil
    2. Institute for Neuroscience and Behavior (INeC), Ribeirão Preto (SP), Brazil
    • Correspondence to: Norberto Cysne Coimbra, Laboratório de Neuroanatomia and Neuropsicobiologia, Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), A. dos Bandeirantes, 3900, Ribeirão Preto (SP), 14049-900, Brasil. E-mail: nccoimbr@fmrp.usp.br

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ABSTRACT

The periaqueductal gray matter (PAG) consists in a brainstem structure rich in 5-hydroxytryptamine (5-HT) inputs related to the modulation of pain. The involvement of each of the serotonergic receptor subtypes found in PAG columns, such as the dorsomedial (dmPAG) and the ventrolateral (vlPAG) columns, regarding post-ictal antinociception have not been elucidated. The present work investigated the participation of the dmPAG and vlPAG columns in seizure-induced antinociception. Specifically, we studied the involvement of serotonergic neurotransmission in these columns on antinociceptive responses that follow tonic-clonic epileptic reactions induced by pentylenetetrazole (PTZ), an ionophore GABA-mediated Cl- influx antagonist. Microinjections of cobalt chloride (1.0 mM CoCl2/0.2 µL) into the dmPAG and vlPAG caused an intermittent local synaptic inhibition and decreased post-ictal antinociception that had been recorded at various time points after seizures. Pretreatments of the dmPAG or the vlPAG columns with the nonselective serotonergic receptors antagonist methysergide (5.0 µg/0.2 µL) or intramesencephalic microinjections of ketanserin (5.0 µg/0.2 µL), a serotonergic antagonist with more affinity to 5-HT2A/2C receptors, decreased tonic-clonic seizure-induced antinociception. Both dmPAG and vlPAG treatment with either the 5-HT2A receptor selective antagonist R-96544 (10 nM/0.2 µL), or the 5-HT2C receptors selective antagonist RS-102221 (0.15 µg/0.2 µL) also decrease post-ictal antinociception. These findings suggest that serotonergic neurotransmission, which recruits both 5-HT2A and 5-HT2C serotonergic receptors in dmPAG and vlPAG columns, plays a critical role in the elaboration of post-ictal antinociception. Synapse, 68:16–30, 2014. © 2013 Wiley Periodicals, Inc.

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