Dual effect of anandamide on spinal nociceptive transmission in control and inflammatory conditions.

Autor: Pontearso M; Laboratory of Pain Research, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic., Slepicka J; Laboratory of Pain Research, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic., Bhattacharyya A; Laboratory of Pain Research, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic., Spicarova D; Laboratory of Pain Research, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic., Palecek J; Laboratory of Pain Research, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic. Electronic address: Jiri.Palecek@fgu.cas.cz.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Apr; Vol. 173, pp. 116369. Date of Electronic Publication: 2024 Mar 06.
DOI: 10.1016/j.biopha.2024.116369
Abstrakt: Anandamide (AEA) is an important modulator of nociception in the spinal dorsal horn, acting presynaptically through Cannabinoid (CB 1 ) and Transient receptor potential vanilloid (TRPV1) receptors. The role of AEA (1 µM, 10 µM, and 30 µM) application on the modulation of nociceptive synaptic transmission under control and inflammatory conditions was studied by recording miniature excitatory postsynaptic currents (mEPSCs) from neurons in spinal cord slices. Inhibition of the CB 1 receptors by PF514273, TRPV1 by SB366791, and the fatty acid amide hydrolase (FAAH) by URB597 was used. Under naïve conditions, the AEA application did not affect the mEPSCs frequency (1.43±0.12 Hz) when all the recorded neurons were considered. The mEPSC frequency increased (180.0±39.2%) only when AEA (30 µM) was applied with PF514273 and URB597. Analysis showed that one sub-population of neurons had synaptic input inhibited (39.1% of neurons), the second excited (43.5%), whereas 8.7% showed a mixed effect and 8.7% did not respond to the AEA. With inflammation, the AEA effect was highly inhibitory (72.7%), while the excitation was negligible (9.1%), and 18.2% were not modulated. After inflammation, more neurons (45.0%) responded even to low AEA by mEPSC frequency increase with PF514273/URB597 present. AEA-induced dual (excitatory/inhibitory) effects at the 1st nociceptive synapse should be considered when developing analgesics targeting the endocannabinoid system. These findings contrast the clear inhibitory effects of the AEA precursor 20:4-NAPE application described previously and suggest that modulation of endogenous AEA production may be more favorable for analgesic treatments.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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