Spinal dorsal horn GABAAreceptors are found both postsynaptically on central neurons and presynaptically on axons and/or terminals of primary sensory neurons, where they mediate primary afferent depolarization (PAD) and presynaptic inhibition. Both phenomena have been studied extensively on a cellular level, but their role in sensory processingin vivohas remained elusive, due to inherent difficulties to selectively interfere with presynaptic receptors. Here, we address the contribution of a major subpopulation of GABAAreceptors (those containing the α2 subunit) to spinal pain control in mice lacking α2-GABAAreceptors specifically in primary nociceptors (sns-α2−/−mice).sns-α2−/−mice exhibited GABAAreceptor currents and dorsal root potentials of normal amplitudein vitro, and normal response thresholds to thermal and mechanical stimulationin vivo, and developed normal inflammatory and neuropathic pain sensitization. However, the positive allosteric GABAAreceptor modulator diazepam (DZP) had almost completely lost its potentiating effect on PAD and presynaptic inhibitionin vitroand a major part of its spinal antihyperalgesic action against inflammatory hyperalgesiain vivo. Our results thus show that part of the antihyperalgesic action of spinally applied DZP occurs through facilitated activation of GABAAreceptors residing on primary nociceptors.