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Dual effect of anandamide on spinal nociceptive transmission in control and inflammatory conditions
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SYSNO ASEP 0583846 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Dual effect of anandamide on spinal nociceptive transmission in control and inflammatory conditions Author(s) Pontearso, Monica (FGU-C) ORCID
Slepička, Jakub (FGU-C) ORCID
Bhattacharyya, Anirban (FGU-C) RID, SAI, ORCID
Špicarová, Diana (FGU-C) RID, ORCID
Paleček, Jiří (FGU-C) RID, ORCIDArticle number 116369 Source Title Biomedicine & Pharmacotherapy. - : Elsevier - ISSN 0753-3322
Roč. 173, April (2024)Number of pages 11 s. Language eng - English Country NL - Netherlands Keywords anandamide ; CB1 ; TRPV1 ; FAAH ; spinal cord ; synaptic transmission OECD category Neurosciences (including psychophysiology R&D Projects GA21-02371S GA ČR - Czech Science Foundation (CSF) GA18-09853S GA ČR - Czech Science Foundation (CSF) LX22NPO5104 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 001203663600001 EID SCOPUS 85187184399 DOI 10.1016/j.biopha.2024.116369 Annotation Anandamide (AEA) is an important modulator of nociception in the spinal dorsal horn, acting presynaptically through Cannabinoid (CB1) 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 CB1 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2025 Electronic address https://doi.org/10.1016/j.biopha.2024.116369
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