20:4-NAPE induced changes of mechanical sensitivity and DRG neurons excitability are concentration dependent and mediated via NAPE-PLD DOI Creative Commons
Anirban Bhattacharyya, Daniel Vasconcelos, Diana Spicarova

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 23, 2025

Abstract Alterations in the excitability of dorsal root ganglion (DRG) neurons are critical pathogenesis acute and chronic pain. Neurotransmitter release from terminals DRG is regulated by cannabinoid receptor 1 (CB ) transient potential vanilloid (TRPV1), both activated anandamide (AEA). In our experiments, AEA precursor N-arachidonoylphosphatidylethanolamine (20:4-NAPE) was used to study modulation nociceptive using K + -evoked Ca 2+ transients. Intrathecal administration evaluate vivo effects. Application 20:4-NAPE at lower concentrations (10 nM − µM) decreased neurons, whereas higher increased it. Both effects were blocked N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor LEI-401. Similarly, externally applied (1 10 nM) inhibited concentration (100 did not change High evoked transients dependent on TRPV1 activation separate experiments. Inhibition CB PF514273 (400 prevented 20:4-NAPE- AEA-induced inhibition, inhibition SB366791 neuron excitability. behavioral tests, caused hyposensitivity, while mechanical allodynia. LEI-401 20:4-NAPE. These results highlight anti- pro-nociceptive mediated concentration-dependent manner. Our underscores complexity endocannabinoid signaling pain transmission highlights as a therapeutic target, offering new insights for developing analgesic strategies.

Language: Английский

20:4-NAPE induced changes of mechanical sensitivity and DRG neurons excitability are concentration dependent and mediated via NAPE-PLD DOI Creative Commons
Anirban Bhattacharyya, Daniel Vasconcelos, Diana Spicarova

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 23, 2025

Abstract Alterations in the excitability of dorsal root ganglion (DRG) neurons are critical pathogenesis acute and chronic pain. Neurotransmitter release from terminals DRG is regulated by cannabinoid receptor 1 (CB ) transient potential vanilloid (TRPV1), both activated anandamide (AEA). In our experiments, AEA precursor N-arachidonoylphosphatidylethanolamine (20:4-NAPE) was used to study modulation nociceptive using K + -evoked Ca 2+ transients. Intrathecal administration evaluate vivo effects. Application 20:4-NAPE at lower concentrations (10 nM − µM) decreased neurons, whereas higher increased it. Both effects were blocked N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor LEI-401. Similarly, externally applied (1 10 nM) inhibited concentration (100 did not change High evoked transients dependent on TRPV1 activation separate experiments. Inhibition CB PF514273 (400 prevented 20:4-NAPE- AEA-induced inhibition, inhibition SB366791 neuron excitability. behavioral tests, caused hyposensitivity, while mechanical allodynia. LEI-401 20:4-NAPE. These results highlight anti- pro-nociceptive mediated concentration-dependent manner. Our underscores complexity endocannabinoid signaling pain transmission highlights as a therapeutic target, offering new insights for developing analgesic strategies.

Language: Английский

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