Anandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level

Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spi...

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Bibliographic Details
Published in:Physiological research 2024-08, Vol.73 (Suppl 1), p.S435-S448
Main Authors: Spicarova, D, Palecek, J
Format: Article
Language:English
Subjects:
Analgesia
Analgesics
Anandamide
Cannabinoid CB1 receptors
Capsaicin receptors
Clinical aspects
Dorsal horn
Enzymes
Fatty acids
Glutamatergic transmission
Glycerol
Kinases
Lipids
Metabolism
Neuromodulation
Pain
Pain perception
Physiology
Review
Sensory neurons
Spinal cord
Synapses
Synaptic transmission
Transient receptor potential proteins
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Summary:Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spinal cord dorsal horn represent an important modulatory site in nociceptive transmission and subsequent pain perception. The glutamatergic synaptic transmission at these synapses is strongly modulated by two primary AEA-activated receptors, cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both highly expressed on the presynaptic side formed by the endings of primary nociceptive neurons. Activation of these receptors can have predominantly inhibitory (CB1) and excitatory (TRPV1) effects that are further modulated under pathological conditions. In addition, dual AEA-mediated signaling and action may occur in primary sensory neurons and dorsal horn synapses. AEA application causes balanced inhibition and excitation of primary afferent synaptic input on superficial dorsal horn neurons in normal conditions, whereas peripheral inflammation promotes AEA-mediated inhibition. This review focuses mainly on the modulation of synaptic transmission at the spinal cord level and signaling in primary nociceptive neurons by AEA via CB1 and TRPV1 receptors. Furthermore, the spinal analgesic effect in preclinical studies and clinical aspects of AEA-mediated analgesia are considered.
ISSN:0862-8408
1802-9973
DOI:10.33549/physiolres.935371