Abstract Patients with Alzheimer’s disease and its related dementias (AD/ADRD), estimated to be >60% of the elderly population, often insufficiently report their pain suffering and are therefore undertreated. This includes orofacial pain suffering that is prevalent in around 10% of patients with dementia and as high as 48.8% of older nursing home residents with dementia . However, little is known if reduced complain of pain in AD/ADRD patients is due to changes in pain processing (sensory-discriminative) or changes in cognitive-evaluative and motivational-affective aspects of pain. Furthermore, a recent study reported sex-specific differences in sensory- discriminative and affective-emotional aspects of pain in an Alzheimer’s disease model (AD- mice). We hypothesize that AD/ADRD and aging may affect physiopathological and/or cognitive/affective aspects of orofacial pain states in a sex-specific manner. This supplemental research is designed to use an automated orofacial testing device to investigate (1) the effects of AD/ADRD and aging in discriminative and cognitive/affective dimensions of orofacial sensation and neuropathic pain processing in male and female AD-mice and aging rats; (2) their sensitivity to anti-orofacial-pain peptide treatments optimized in the parent grant research. Successful completion of the proposed research will allow us to determine if the physiopathology and/or cognitive/affective aspects of orofacial sensitivity as well as orofacial sensitivity to anti-orofacial- pain peptide treatments are modulated by AD/ADRD and aging in a sex-specific manner. Therefore, this supplemental research is relevant to AD/ADRD and within the scope of the parent award that is not currently focused on Alzheimer’s disease. Promising data generated from this investigation will be used to form the basis for new investigations through competing grant applications in the field of neurobiology/pharmacology related to AD/ADRD and orofacial pain.