Neuropharmacology

 

Atypical GABA Receptors in Pain Circuits

 

Neumann et al.

Inhibitory GABA_A receptors in the central nervous system are usually composed of two alpha, two beta, and one gamma subunits. These subunits are heterogeneous: there are six different alpha subtypes, three beta subtypes, and three gamma subtypes. The composition of GABA_A receptors is important clinically because the subunits can be distinctly targeted by treatments for different disease symptoms. Benzodiazepines (BDZs) target GABA_A receptors, strengthening their signaling. Alpha subunits and gamma subunits together contribute to BDZ binding on GABA_A receptors, but gamma subunits have received less research attention. Neumann and colleagues address this oversight. They identified a unique GABA_A receptor in the spinal dorsal horn, a key site for pain processing. Using mice, the authors found that gamma 1-containing GABA_A receptors were highly expressed in this region. Furthermore, they sufficiently supported synaptic clustering of GABA_A receptors and BDZ action when gamma 2-containing GABA_A receptors in the spinal cord were ablated. These findings suggest that gamma 1-containing GABA_A receptors contribute to functionally relevant pain processing circuits. This is a major preclinical advancement and may inform treatment development for pain.