β-amyloid is an important factor in the pathophysiology of Alzheimer's disease. This study investigates β-amyloid's role in the regulation of nociception in mice. Pretreated once, 2 weeks prior to testing with β-amyloid, male ICR mice were examined on various nociceptive tests. Pretreatment with β-amyloid reversed the nociceptive effects induced by intraperitoneally administered acetic acid (writhing response) and intraplantar injection of 5% formalin into the hind paw. β-amyloid pretreatment also elevated the threshold for nociception in the mechanical von Frey test. Additionally, p-CREB and p-ERK levels in the spinal cord and the adrenal gland increased after formalin injection. Pretreatment with β-amyloid attenuated formalin‑induced overexpression of p-CREB and p-ERK in the spinal cord and the adrenal gland. Our results suggest that chemical and mechanical nociception appear to be altered in β-amyloid-treated animals. Furthermore, the reduction of nociception by β-amyloid in the formalin pain model appears to be mediated, at least in part, by the suppression of p-CREB and p-ERK level in the spinal cord and the adrenal gland.