GABA signaling in peripheral sensory neurons: a potential role in inflammatory pain

Abstract

Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) neurons through GABAA receptor activation.

In the present study, we tested whether GABAA receptors are involved in nociceptive signaling and pain behavior during formalin-induced acute inflammatory pain in adult mice. We found that peripheral administration of the GABAA receptor agonist, muscimol, restored spontaneous licking behavior after subsidence of formalin-induced pain behavior.

We performed extracellular single-unit recordings from spinal cord wide dynamic range neurons in vivo and showed that spike frequency was increased by muscmiol injection into hind paw after, but not before, formalin treatment.

Using Ca2+ imaging in vitro we show that formalin, as well as the major inflammatory mediator prostaglandin E2, can potentiate GABA-induced Ca2+ transients in cultured DRG neurons, an effect that is blocked by the prostaglandin EP4 receptor antagonist AH23848.

Taken together, these results demonstrated that GABAA receptors may contribute to excitation of peripheral sensory neurons in inflammation through PGE2-EP4 signaling.