Top

Published in:

01-03-2015 | Neurology and Preclinical Neurological Studies - Short communication

Intracisternal injection of palmitoylethanolamide inhibits the peripheral nociceptive evoked responses of dorsal horn wide dynamic range neurons

Authors: Abimael González-Hernández, Guadalupe Martínez-Lorenzana, Javier Rodríguez-Jiménez, Gerardo Rojas-Piloni, Miguel Condés-Lara

Published in: Journal of Neural Transmission | Issue 3/2015

Abstract

Endogenous palmitoylethanolamide (PEA) has a key role in pain modulation. Central or peripheral PEA can reduce nociceptive behavior, but no study has yet reported a descending inhibitory effect on the neuronal nociceptive activity of Aδ- and C-fibers. This study shows that intracisternal PEA inhibits the peripheral nociceptive responses of dorsal horn wide dynamic range cells (i.e., inhibition of Aδ- and C-fibers), an effect blocked by spinal methiothepin. These results suggest that a descending analgesic mechanism mediated by the serotonergic system could be activated by central PEA.

Andrade R, Barnes NM, Baxter G, Bockaert J, Branchek T, Cohen ML, Dumuis A, Eglen RM, Göthert M, Hamblin M, Hamon M, Hartig PR, Hen R, Herrick-Davis K, Hills R, Hoyer D, Humphrey PA, Latté KP, Maroteaux L, Martin GR, Middlemiss DN, Mylecharane E, Peroutka SJ, Saxena PR, Sleight A, Villalon CM, Yocca F (2014) 5-Hydroxytryptamine receptors. IUPHAR database (IUPHAR-DB). Available at: http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=1. Accessed on 02/05/2014

Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P (2010) Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. Pain Med 11:781–784CrossRefPubMed

Calignano A, La Rana G, Giuffrida A, Piomelli D (1998) Control of pain initiation by endogenous cannabinoids. Nature 394:277–281CrossRefPubMed

Calignano A, La Rana G, Piomelli D (2001) Antinociceptive activity of the endogenous fatty acid amide, palmitoylethanolamide. Eur J Pharmacol 419:191–198CrossRefPubMed

Condés-Lara M, Marina-González N, Martínez-Lorenzana G, Luis-Delgado O, Freund-Mercier MJ (2003) Actions of oxytocin and interactions with glutamate on spontaneous and evoked dorsal spinal cord neuronal activities. Brain Res 976:75–81CrossRefPubMed

Condés-Lara M, Maie IA, Dickenson AH (2005) Oxytocin actions on afferent evoked spinal cord neuronal activities in neuropathic but not in normal rats. Brain Res 1045:124–133CrossRefPubMed

Conigliaro R, Drago V, Foster PS, Schievano C, Di Marzo V (2011) Use of palmitoylethanolamide in the entrapment neuropathy of the median in the wrist. Minerva Med 102:141–147PubMed

D’Agostino G, La Rana G, Russo R, Sasso O, Iacono A, Esposito E, Raso GM, Cuzzocrea S, Lo Verme J, Piomelli D, Meli R, Calignano A (2007) Acute intracerebroventricular administration of palmitoylethanolamide, an endogenous peroxisome proliferator-activated receptor-alpha agonist, modulates carrageenan-induced paw edema in mice. J Pharmacol Exp Ther 322:1137–1143CrossRefPubMed

D’Agostino G, La Rana G, Russo R, Sasso O, Iacono A, Esposito E, Mattace Raso G, Cuzzocrea S, Loverme J, Piomelli D, Meli R, Calignano A (2009) Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-kappaB nuclear signalling in dorsal root ganglia. Eur J Pharmacol 613:54–59CrossRefPubMed

de Novellis V, Palazzo E, Rossi F, De Petrocellis L, Petrosino S, Guida F, Luongo L, Migliozzi A, Cristino L, Marabese I, Starowicz K, Di Marzo V, Maione S, Endocannabinoid Research Group (2008) The analgesic effect of N-arachidonoyl-serotonin, a FAAH inhibitor and TRPV1 receptor antagonist, associated with changes in rostral ventromedial medulla and locus coeruleus cell activity in rats. Neuropharmacology 55:1105–1113CrossRefPubMed

Dogrul A, Ossipov MH, Porreca F (2009) Differential mediation of descending pain facilitation and inhibition by spinal 5-HT3 and 5-HT7 receptors. Brain Res 1280:52–59CrossRefPubMed

Esposito E, Paterniti I, Mazzon E, Genovese T, Di Paola R, Cuzzocrea S (2011) Effects of palmitoylethanolamide on mast cell mediator release and neurotrophic factors in experimental model of spinal cord injury. Brain Behav Immun 25:1099–1112CrossRefPubMed

Gatti A, Lazzari M, Gianfelice V, Di Paolo A, Sabato E, Sabato AF (2012) Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis. Pain Med 13:1121–1130CrossRefPubMed

Genovese T, Esposito E, Mazzon E, Di Paola R, Meli R, Bramanti P, Piomelli D, Calignano A, Cuzzocrea S (2008) Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury. J Pharmacol Exp Ther 326:12–23CrossRefPubMed

Hammond DL, Yaksh TL (1981) Peripheral and central pathways in pain. Pharmacol Ther 14:459–475CrossRefPubMed

Jaggar SI, Hasnie FS, Sellaturay S, Rice AS (1998) The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain. Pain 76:189–199CrossRefPubMed

Lambert DM, Di Marzo V (1999) The palmitoylethanolamide and oleamide enigmas: are these two fatty acids cannabimimetic? Curr Med Chem 6:757–773PubMed

Loría F, Petrosino S, Mestre L, Spagnolo A, Correa F, Hernangómez M, Marzo Di, Docagne F (2008) Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide. Eur J Neurosci 28:633–641CrossRefPubMed

LoVerme J, Fu J, Astarita G, La Rana G, Russo R, Calignano A, Piomelli D (2005a) The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol 67:15–29CrossRef

LoVerme J, La Rana G, Russo R, Calignano A, Piomelli D (2005b) The search for the palmitoylethanolamide receptor. Life Sci 77:1685–1698CrossRefPubMed

LoVerme J, Russo R, La Rana G, Fu J, Farthing J, Mattace-Raso G, Meli R, Hohmann A, Calignano A, Piomelli D (2006) Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha. J Pharmacol Exp Ther 319:1051–1061CrossRefPubMed

Sasaki M, Ishizaki K, Obata H, Goto F (2001) Effects of 5-HT2 and 5-HT3 receptors on the modulation of nociceptive transmission in rat spinal cord according to the formalin test. Eur J Pharmacol 424:45–52CrossRefPubMed

Schmidtko A, Tegeder I, Geisslenger G (2009) No no, no pain? The role of nitric oxide and cGMP in spinal pain processing. Trends Neurosci 32:339–346CrossRefPubMed

Seyrek M, Kahraman S, Deveci MS, Yesilyurt O, Dogrul A (2010) Systemic cannabinoids produce CB₁-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT₇ and 5–HT_2A receptors. Eur J Pharmacol 649:183–194CrossRefPubMed

Skaper SD, Facci L (2012) Mast cell-glia axis in neuroinflammation and therapeutic potential of the anandamide congener. Philos Trans R Soc Lond B Biol Sci 367:3312–3325CrossRefPubMedCentralPubMed

Walker JM, Krey JF, Chu CJ, Huang SM (2002) Endocannabinoids and related fatty acid derivatives in pain modulation. Chem Phys Lipids 121:159–172CrossRefPubMed

Willingale HL, Gardiner NJ, McLymont N, Giblett S, Grubb BD (1997) Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol 122:1593–1604CrossRefPubMedCentralPubMed

Zimmermann M (1983) Ethical guidelines for investigation of experimental pain in conscious animals. Pain 16:109–110CrossRefPubMed

Title: Intracisternal injection of palmitoylethanolamide inhibits the peripheral nociceptive evoked responses of dorsal horn wide dynamic range neurons
Authors: Abimael González-Hernández
Guadalupe Martínez-Lorenzana
Javier Rodríguez-Jiménez
Gerardo Rojas-Piloni
Miguel Condés-Lara
Publication date: 01-03-2015
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 3/2015
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-014-1255-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Intracisternal injection of palmitoylethanolamide inhibits the peripheral nociceptive evoked responses of dorsal horn wide dynamic range neurons

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2015

A molecular pathway analysis of the glutamatergic–monoaminergic interplay serves to investigate the number of depressive records during citalopram treatment

Sequencing and expression analyses of the synaptic lipid raft adapter gene PAG1 in schizophrenia

Stiff person-syndrome IgG affects presynaptic GABAergic release mechanisms

Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice

Blepharospasm: long-term treatment with either Botox®, Xeomin® or Dysport®

The development of the N1 and N2 components in auditory oddball paradigms: a systematic review with narrative analysis and suggested normative values