Peripheral nerve damage and inflammation induce alterations in synaptic inhibition in neuronal circuits of the spinal dorsal horn through a variety of different processes, including changes in the transmembrane chloride gradient of dorsal horn neurons, changes in the synthesis of neurotransmitters and alterations in the function of neurotransmitter receptors (for a review see Zeilhofer et al., 2012). Such impaired inhibition commonly leads to pathologic pain syndromes manifesting in the development of hyperalgesia and allodynia, and possibly also in compromised spinal motor control. During the last five years our group has worked on the identification of pharmacological targets that would allow to restore compromised neuronal inhibition without the typical unwanted effects of typical GABAergic compounds such as the classical benzodiazepines. Using a series of GABA-A receptor point mutated mice we could demonstrate that the selective activation of GABA-A receptors containing alpha2 subunits can alleviate sensory symptoms of impaired spinal synaptic inhibition without inducing sedation (Zeilhofer et al., 2009). Other at present still underexplored possibilities may include the pharmacological potentiation of inhibitory glycine receptors (Yevenes & Zeilhofer, 2011). Recent work indicates that certain structural analogues of endocannabinoids act as allosteric modulators of inhibitory glycine receptors. Evidence from different groups suggests that such compounds also reverse pathological pain syndromes in different rodent models.