Effects of intra-ventrolateral periaqueductal grey palmitoylethanolamide on thermoceptive threshold and rostral ventromedial medulla cell activity

Vito de Novellis, Livio Luongo, Francesca Guida, Luigia Cristino, Enza Palazzo, Roberto Russo, Ida Marabese, Giuseppe D'Agostino, Antonio Calignano, Francesca Rossi, Vincenzo Di Marzo, Sabatino Maione

Research output: Contribution to journalArticle

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Abstract

Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α (PPAR-α) ligand, exerts antinociceptive and anti-inflammatory effects. PEA (3 and 6 nmol) was microinjected in the ventrolateral periaqueductal grey (VL PAG) of male rats and effects on nociceptive responses and ongoing and tail flick-related activities of rostral ventromedial medulla (RVM) ON and OFF cells were recorded. Intra-PAG microinjection of PEA reduced the ongoing activity of ON and OFF cells and produced an increase in the latency of the nociceptive reaction. These effects were prevented by a selective PPAR-α antagonist, GW6471 and by a large-conductance Ca(2+)-activated K(+) channel inhibitor, charybdotoxin. Cannabinoid 1 (CB(1)) receptor blockade by AM251 increased the PEA-induced effect both on the ongoing activity of the ON cell and on the latency to tail flick without affecting the effect of PEA on the OFF cell. Conversely, a transient receptor potential vanilloid type 1 (TRPV(1)) blocker, I-RTX, had no effect on the ON cell activity and tail flick latency, whereas it blocked the PEA-induced decrease in ongoing activity of the OFF cell. PEA decreased the burst and increased the latency of tail flick-evoked onset of ON cell activity in a manner antagonised by GW6471 and charybdotoxin. AM251 and I-RTX, instead, enhanced these latter effects. In conclusion, intra-VL PAG PEA induces antinociceptive effects associated with a decrease in RVM ON and OFF cell activities. PPAR-α receptors mediate, and CB(1) and TRPV(1) receptors antagonise, PEA-induced effects within the PAG-RVM circuitry.
Original languageEnglish
Pages (from-to)41-50
Number of pages10
JournalEuropean Journal of Pharmacology
Volume676
Issue number1-3
Early online date3 Dec 2011
DOIs
Publication statusPublished - 15 Feb 2012

Fingerprint

Periaqueductal Gray
Peroxisome Proliferator-Activated Receptors
Tail
Charybdotoxin
palmidrol
Cannabinoids
Microinjections
Anti-Inflammatory Agents
Ligands

Keywords

  • analgesics
  • animals
  • behavior, animal
  • endocannabinoids
  • ethanolamines
  • gene expression regulation
  • male
  • myelencephalon
  • neurons
  • nociception
  • PPAR alpha
  • palmitic acids
  • periaqueductal gray
  • potassium channels, calcium-activated
  • rats
  • rats, wistar
  • receptor, cannabinoid, CB1
  • TRPV cation channels
  • temperature

Cite this

Effects of intra-ventrolateral periaqueductal grey palmitoylethanolamide on thermoceptive threshold and rostral ventromedial medulla cell activity. / de Novellis, Vito; Luongo, Livio; Guida, Francesca; Cristino, Luigia; Palazzo, Enza; Russo, Roberto; Marabese, Ida; D'Agostino, Giuseppe; Calignano, Antonio; Rossi, Francesca; Di Marzo, Vincenzo; Maione, Sabatino.

In: European Journal of Pharmacology, Vol. 676, No. 1-3, 15.02.2012, p. 41-50.

Research output: Contribution to journalArticle

de Novellis, V, Luongo, L, Guida, F, Cristino, L, Palazzo, E, Russo, R, Marabese, I, D'Agostino, G, Calignano, A, Rossi, F, Di Marzo, V & Maione, S 2012, 'Effects of intra-ventrolateral periaqueductal grey palmitoylethanolamide on thermoceptive threshold and rostral ventromedial medulla cell activity' European Journal of Pharmacology, vol. 676, no. 1-3, pp. 41-50. https://doi.org/10.1016/j.ejphar.2011.11.034
de Novellis, Vito ; Luongo, Livio ; Guida, Francesca ; Cristino, Luigia ; Palazzo, Enza ; Russo, Roberto ; Marabese, Ida ; D'Agostino, Giuseppe ; Calignano, Antonio ; Rossi, Francesca ; Di Marzo, Vincenzo ; Maione, Sabatino. / Effects of intra-ventrolateral periaqueductal grey palmitoylethanolamide on thermoceptive threshold and rostral ventromedial medulla cell activity. In: European Journal of Pharmacology. 2012 ; Vol. 676, No. 1-3. pp. 41-50.
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abstract = "Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α (PPAR-α) ligand, exerts antinociceptive and anti-inflammatory effects. PEA (3 and 6 nmol) was microinjected in the ventrolateral periaqueductal grey (VL PAG) of male rats and effects on nociceptive responses and ongoing and tail flick-related activities of rostral ventromedial medulla (RVM) ON and OFF cells were recorded. Intra-PAG microinjection of PEA reduced the ongoing activity of ON and OFF cells and produced an increase in the latency of the nociceptive reaction. These effects were prevented by a selective PPAR-α antagonist, GW6471 and by a large-conductance Ca(2+)-activated K(+) channel inhibitor, charybdotoxin. Cannabinoid 1 (CB(1)) receptor blockade by AM251 increased the PEA-induced effect both on the ongoing activity of the ON cell and on the latency to tail flick without affecting the effect of PEA on the OFF cell. Conversely, a transient receptor potential vanilloid type 1 (TRPV(1)) blocker, I-RTX, had no effect on the ON cell activity and tail flick latency, whereas it blocked the PEA-induced decrease in ongoing activity of the OFF cell. PEA decreased the burst and increased the latency of tail flick-evoked onset of ON cell activity in a manner antagonised by GW6471 and charybdotoxin. AM251 and I-RTX, instead, enhanced these latter effects. In conclusion, intra-VL PAG PEA induces antinociceptive effects associated with a decrease in RVM ON and OFF cell activities. PPAR-α receptors mediate, and CB(1) and TRPV(1) receptors antagonise, PEA-induced effects within the PAG-RVM circuitry.",
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AU - de Novellis, Vito

AU - Luongo, Livio

AU - Guida, Francesca

AU - Cristino, Luigia

AU - Palazzo, Enza

AU - Russo, Roberto

AU - Marabese, Ida

AU - D'Agostino, Giuseppe

AU - Calignano, Antonio

AU - Rossi, Francesca

AU - Di Marzo, Vincenzo

AU - Maione, Sabatino

N1 - Copyright © 2011 Elsevier B.V. All rights reserved.

PY - 2012/2/15

Y1 - 2012/2/15

N2 - Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α (PPAR-α) ligand, exerts antinociceptive and anti-inflammatory effects. PEA (3 and 6 nmol) was microinjected in the ventrolateral periaqueductal grey (VL PAG) of male rats and effects on nociceptive responses and ongoing and tail flick-related activities of rostral ventromedial medulla (RVM) ON and OFF cells were recorded. Intra-PAG microinjection of PEA reduced the ongoing activity of ON and OFF cells and produced an increase in the latency of the nociceptive reaction. These effects were prevented by a selective PPAR-α antagonist, GW6471 and by a large-conductance Ca(2+)-activated K(+) channel inhibitor, charybdotoxin. Cannabinoid 1 (CB(1)) receptor blockade by AM251 increased the PEA-induced effect both on the ongoing activity of the ON cell and on the latency to tail flick without affecting the effect of PEA on the OFF cell. Conversely, a transient receptor potential vanilloid type 1 (TRPV(1)) blocker, I-RTX, had no effect on the ON cell activity and tail flick latency, whereas it blocked the PEA-induced decrease in ongoing activity of the OFF cell. PEA decreased the burst and increased the latency of tail flick-evoked onset of ON cell activity in a manner antagonised by GW6471 and charybdotoxin. AM251 and I-RTX, instead, enhanced these latter effects. In conclusion, intra-VL PAG PEA induces antinociceptive effects associated with a decrease in RVM ON and OFF cell activities. PPAR-α receptors mediate, and CB(1) and TRPV(1) receptors antagonise, PEA-induced effects within the PAG-RVM circuitry.

AB - Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-α (PPAR-α) ligand, exerts antinociceptive and anti-inflammatory effects. PEA (3 and 6 nmol) was microinjected in the ventrolateral periaqueductal grey (VL PAG) of male rats and effects on nociceptive responses and ongoing and tail flick-related activities of rostral ventromedial medulla (RVM) ON and OFF cells were recorded. Intra-PAG microinjection of PEA reduced the ongoing activity of ON and OFF cells and produced an increase in the latency of the nociceptive reaction. These effects were prevented by a selective PPAR-α antagonist, GW6471 and by a large-conductance Ca(2+)-activated K(+) channel inhibitor, charybdotoxin. Cannabinoid 1 (CB(1)) receptor blockade by AM251 increased the PEA-induced effect both on the ongoing activity of the ON cell and on the latency to tail flick without affecting the effect of PEA on the OFF cell. Conversely, a transient receptor potential vanilloid type 1 (TRPV(1)) blocker, I-RTX, had no effect on the ON cell activity and tail flick latency, whereas it blocked the PEA-induced decrease in ongoing activity of the OFF cell. PEA decreased the burst and increased the latency of tail flick-evoked onset of ON cell activity in a manner antagonised by GW6471 and charybdotoxin. AM251 and I-RTX, instead, enhanced these latter effects. In conclusion, intra-VL PAG PEA induces antinociceptive effects associated with a decrease in RVM ON and OFF cell activities. PPAR-α receptors mediate, and CB(1) and TRPV(1) receptors antagonise, PEA-induced effects within the PAG-RVM circuitry.

KW - analgesics

KW - animals

KW - behavior, animal

KW - endocannabinoids

KW - ethanolamines

KW - gene expression regulation

KW - male

KW - myelencephalon

KW - neurons

KW - nociception

KW - PPAR alpha

KW - palmitic acids

KW - periaqueductal gray

KW - potassium channels, calcium-activated

KW - rats

KW - rats, wistar

KW - receptor, cannabinoid, CB1

KW - TRPV cation channels

KW - temperature

U2 - 10.1016/j.ejphar.2011.11.034

DO - 10.1016/j.ejphar.2011.11.034

M3 - Article

VL - 676

SP - 41

EP - 50

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -