Journal
BRITISH JOURNAL OF ANAESTHESIA
Volume 120, Issue 6, Pages 1315-1334Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.bja.2018.02.066
Keywords
alpha 2-delta subunit 1 protein; gamma-aminobutyric acid; pregabalin
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The focus of perioperative pain management should be to attempt to minimise the nociceptive input and reduce the risk of transition to central sensitisation. Gabapentinoids are being increasingly used as adjuncts for management of perioperative pain. Although gabapentinoids are classed as calcium channel blockers, their mechanisms of action are poorly understood. The analgesic effect in neuropathic pain is well evidenced but the role in postoperative pain is less certain. Medline and EMBASE database searches were conducted to identify studies relating to mechanisms of action and effects in experimental animal models of inflammatory and postoperative pain and human models of experimental pain. The effects of gabapentinoids may be attributed to depression of dorsal horn sensitivity through a multitude of mechanisms. They inhibit calcium mediated neurotransmitter release through effects on alpha 2 delta-1 subunits. They inhibit forward trafficking of alpha 2 delta-1 from the dorsal root ganglion, their recycling from endosomal compartments, thrombospondin mediated processes and stimulate glutamate uptake by excitatory amino acid transporters. 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. Gabapentinoids are effective analgesics in most animal models of inflammation and postoperative pain but effects in human models are variable.
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