Research has shown that individuals with Down syndrome experience altered pain sensitivity, with varying results depending on the type of nociceptive stimulus. GRIK1, a gene coding for the GluK1 subunit of kainate receptors is triplicated in Down syndrome. This subunit is heavily expressed in Dorsal Root Ganglion neurons and has been implicated in modulating pain perception. To investigate this further, we have conducted experiments in the Ts2Cje mouse model of Down syndrome, comparing them to mice lacking Grik1. The results suggest that altered pain perception in Down syndrome is dependent on Grik1 overexpression and that this subunit plays a crucial role in the sensitivity to nociceptive stimulation. These results shed light on the underlying mechanisms of abnormal pain perception in Down syndrome individuals and may help in the development of more targeted treatments for this condition.