Mice lacking spinal α2GABAA receptors: Altered GABAergic neurotransmission, diminished GABAergic antihyperalgesia, and potential compensatory mechanisms preventing a hyperalgesic phenotype.

Mice lacking spinal α2GABAA receptors: Altered GABAergic neurotransmission, diminished GABAergic antihyperalgesia, and potential compensatory mechanisms preventing a hyperalgesic phenotype.
Brain Res. 2020 May 18;:146889
Authors: Tudeau L, Acuña MA, Albisetti GW, Neumann E, Ralvenius WT, Scheurer L, Poe M, Cook JM, Johannssen HC, Ulrich Zeilhofer H
Abstract
Diminished synaptic inhibition in the superficial spinal dorsal horn contributes to exaggerated pain responses that accompany peripheral inflammation and neuropathy. α2GABAA receptors (α2GABAAR) constitute the most abundant GABAAR subtype at this site and are the targets of recently identified antihyperalgesic compounds. Surprisingly, hoxb8-α2-/- mice that lack α2GABAAR from the spinal cord and peripheral sensory neurons exhibit unaltered sensitivity to acute painful stimuli and develop normal inflammatory and neuropathic hyperalgesia. Here, we provide a comprehensive analysis of GABAergic neurotransmission, of behavioral phenotypes and of possible compensatory mechanisms in hoxb8-α2-/- mice. Our results confirm that hoxb8-α2-/- mice show significantly diminished GABAergic inhibitory postsynaptic currents (IPSCs) in the superficial dorsal horn but no hyperalgesic phenotype. We also confirm that the potentiation of dorsal horn GABAergic IPSCs by the α2-preferring GABAAR modulator HZ-166 is reduced in hoxb8-α2-/- mice and that hoxb8-α2-/- mice are resistant to the analges...

Source: Brain Research - May 17, 2020 Category: Neurology Authors: Tudeau L, Acuña MA, Albisetti GW, Neumann E, Ralvenius WT, Scheurer L, Poe M, Cook JM, Johannssen HC, Ulrich Zeilhofer H Tags: Brain Res Source Type: research