Central post-stroke pain (CPSP) is defined as unbearable neuropathic pain that can subacutely occur after hemorrhage or ischemic cerebrovascular diseases in some central nervous regions, such as the thalamus and putamen. Since the pathophysiological mechanism underlying CPSP remains unclear, effective therapeutic targets are currently very limited. Recently, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) and its specific receptor (PAC1R) played an important role in the onset and maintenance of peripheral neuropathic pain, and therefore we developed novel small-molecule antagonists of PAC1R (PA-8, PA-915, etc.) using docking-based in-silico screening. Here, we attempted to analyze the association of CPSP and PACAP/PAC1R signaling using a thalamic hemorrhage mouse model. Intraperitoneal injections of PA-8 or PA-915 attenuated the hemorrhage-induced mechanical allodynia and astroglial activations in a dose-dependent manner. Furthermore, PACAP^-/- mice also developed reduced mechanical allodynia after thalamic hemorrhage. These results suggest that PACAP/PAC1R-evoked astroglial activation contributes to the thalamic hemorrhage-induced nociceptive behavior, and PAC1R antagonist can be a potential analgesic for CPSP.