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  • Title: GABAergic analgesia: new insights from mutant mice and subtype-selective agonists.
    Author: Zeilhofer HU, Möhler H, Di Lio A.
    Journal: Trends Pharmacol Sci; 2009 Aug; 30(8):397-402. PubMed ID: 19616317.
    Abstract:
    Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the brain where it regulates many physiological functions including sleep, anxiety, reward and memory formation. GABAergic neurons and ionotropic GABA(A) receptors are also found in the spinal cord dorsal horn where they control the propagation of pain signals from the periphery to higher central nervous system areas. Recent evidence indicates that diminished inhibitory control at this site is a major factor in chronic pain syndromes. So far, this knowledge could not be translated into clinical pain therapy, probably because of the widespread actions of GABA in the central nervous system. The identification of GABA(A) receptor subtypes responsible for spinal antihyperalgesic effects has recently opened new avenues for the development of subtype-selective modulators of GABA(A) receptors. First results raise hopes that such compounds will be active against inflammatory and neuropathic pain but devoid of many of the side-effects of the established benzodiazepine-like drugs.
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