Systemically and centrally delivered opioids have been comprehensively studied for their effects both in analgesic and addiction models for many decades, primarily in subjects with presumptive normal sensory thresholds. The introduction of disease-based models of persistent hypersensitivity enabled chronic evaluation of opioid analgesic pharmacology under the specific state of chronic pain. These studies have largely (but not uniformly) reported reduced opioid analgesic potency and efficacy under conditions of chronic pain. A comparatively limited set of studies has evaluated the impact of experimentally induced chronic pain on self-administration patterns of opioid and non-opioid analgesics. Similarly, these studies have primarily (but not exclusively) found that responding for opioids is reduced under conditions of chronic pain. Additionally, such experiments have also demonstrated that the condition of chronic pain evokes self-administration or conditioned place preference for non-opioid analgesics. The consensus is that the chronic pain alters responding for opioid and non-opioid analgesics in a manner seemingly related to their respective antiallodynic/antihyperalgesic properties under the specific state of chronic pain.