Aim: We explored the role of the GABAB auxiliary subunit KCTD16 in nociceptive synaptic transmission in naïve mice and in model of peripheral inflammation.Methods: KCTD16 -/- KO mice (obtained from B. Bettler, Uni Basel) WT and the transgenic mice (VGAT-ChR2-EYFP crossed with KCTD16 KO) were used. Behavioral testing of mechanical (von Frey filament) and thermal (hot plate) sensitivity, patch clamp recordings from dorsal horn neurons in spinal cord slices (miniature postsynaptic excitatory currents mEPSC, light evoked inhibitory currents leIPSC) were used. Inflammation was induced by intraplantar 1% carrageenan injection.Results: Our data show that KCTD16-/- and WT animals have the same thermal sensitivity, while the mechanical threshold is higher in the KCTD16-/- mice. The treatment with GABAB agonist (Baclofen) produced stronger analgesic effect in the WT mice compared to the KO littermates in controls and also after inflammation. Baclofen application had higher inhibitory effect on mEPSC frequency in WT animals, especially after inflammation. The inhibitory effect of baclofen on leIPSC was highly reduced after inflammation in the WT animals, but was minimally changed in the KCTD16-/- neurons.Conclusion: Modulation of nociception by the KCTD16 protein is important especially after GABAB receptors activation. This GABAB mediated inhibitory effect is attenuated in the KCTD16-/- animals where disruption of the GABAB-KCTD16 complex possibly affects the forward signaling by GIRK, VGCC, adenylyl cyclase and HCN channels. Further experiments are needed to understand the role of the GABABR regulatory protein KCTD16 in nociception. Supported by GACR 21-17085S and GAUK 198923.