The aim of this paper was to evaluate the interactions of Somatostatin receptor-2 (SST2) and Neuropeptide Y receptors-1 (Y1) by molecular, pharmacological and behavioral studies. Double-immunolabeling of SST2 and Y1 has shown the colocalization of these two receptors in the dorsal root ganglion (DRG) neurons. On the basis of the Pinch nerve injury model, the mechanical hyperalgesia and severely painful behavior (autotomy) were detected after the application of SST2 antibody (anti-SST2; 200μg/kg) on the pinch-injured nerve. The differential distribution of Y1 and up-regulation of PKC expression in DRGs were observed after anti-SST2 treatment. Our results indicated for the first time the interactions of SST2 and Y1 in DRGs, which have functional role in pain modulation and might give rise to explore possible novel therapeutic strategies against pain.