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

Author(s)

de Freitas, Renato Leonardo ^{[1, 2]} ; de Oliveira, Rithiele Cristina ^{[1, 2]} ; de Oliveira, Ricardo ^{[1, 2]} ; Paschoalin-Maurin, Tatiana ^{[1, 2]} ; de Aguiar Correa, Fernando Morgan ^[3] ; Coimbra, Norberto Cysne ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Inst Neurosci & Behav INeC, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Lab Cent Control Arterial Pressure, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Synapse; v. 68, n. 1, p. 16-30, JAN 2014.
• Web of Science Citations: 14

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 postictal 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 mu L) 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 mu g/0.2 mu L) or intramesencephalic microinjections of ketanserin (5.0 mu g/0.2 mu L), 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 mu L), or the 5-HT2C receptors selective antagonist RS-102221 (0.15 mu g/0.2 mu L) 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. (C) 2013 Wiley Periodicals, Inc. (AU)

• FAPESP's process: 09/00668-6 - Study of the involvement of cholinergic pathways form tegmentar pedunculopontine nucleus to monoaminergic nuclei of the pain endogenous inhibitory system in the post-ictal antinociception
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants