M. Chincholkar British Journal of Anaesthesia

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Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review M. Chincholkar British Journal of Anaesthesia Volume 120, Issue 6, Pages 1315-1334 (June 2018) DOI: 10.1016/j.bja.2018.02.066 Copyright © 2018 British Journal of Anaesthesia Terms and Conditions

Fig 1 Voltage-gated calcium channels are composed of four subunits. The α1 subunit consists of four homologous domains, each containing six transmembrane segments. It is the pore-forming subunit. The β subunit is intracellular. The γ subunit has four transmembrane segments. The δ subunit has one transmembrane segment and is attached to the extracellular α2 subunit via a disulfide bond. Reprinted, with permission, from Elsevier.10 British Journal of Anaesthesia 2018 120, 1315-1334DOI: (10.1016/j.bja.2018.02.066) Copyright © 2018 British Journal of Anaesthesia Terms and Conditions

Fig 2 Gabapentinoids inhibit calcium mediated neurotransmitter release through effects on α2δ-1 subunits. They inhibit forward trafficking of α2δ-1 from the dorsal root ganglion, their recycling from endosomal compartments, thrombospondin mediated processes and stimulate glutamate uptake by excitatory amino acid transporters (EAAT). Mechanisms not directly related to neurotransmitter release at dorsal horn include inhibition of descending serotonergic facilitation, stimulation of descending inhibition, anti-inflammatory actions and influence on the affective component of pain. British Journal of Anaesthesia 2018 120, 1315-1334DOI: (10.1016/j.bja.2018.02.066) Copyright © 2018 British Journal of Anaesthesia Terms and Conditions