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Antinociceptive and nociceptive responses can be elicited by the administration of {dollar}\\beta{dollar}-endorphin within the periaqueductal gray region of the midbrain. The pain inhibitory and facilitory systems exist in a state of balance such that under most conditions, the combined activation of these processes by the administration of {dollar}\\beta{dollar}-endorphin results in the expression of antinociception. However, during other situations, such as stress, the delicate balance between these endogenous systems is disrupted and alterations in the overall response to opioids occurs. When stress is minimized the contribution of the {dollar}\\beta{dollar}-endorphin dependent pain facilitory systems is minimal and cannot be discriminated unless a low dose of the opioid antagonist, CTP is co-administered into the PAG. In this instance, the blockade of the pain facilitory processes results in an enhancement of {dollar}\\beta{dollar}-endorphin induced antinociception. The receptors through which the pain facilitory actions of {dollar}\\beta{dollar}-endorphin are mediated appear to be unique. They possess a much higher relative affinity (30 to 100 fold) for opioid receptor antagonists as compared to those receptors which modulate the pain inhibitory processes and their pharmacological profiles do not coincide with the classical {dollar}\\rm\\mu,\\ \\delta,\\ or\\ \\kappa{dollar} receptors. When animals are repetitively exposed to noxious heat, a "non-opioid" stress-induced analgesia develops, but the potency of {dollar}\\beta{dollar}-endorphin in the PAG is reduced, and pain facilitation is observed at low (30 pmol) doses of {dollar}\\beta{dollar}-endorphin. This facilitory component, which is more easily observed during stress, is sensitive to slightly higher doses of CTP and naltrexone. Thus, it seems that during stress, even though analgesia is expressed, the contribution of opioid-dependent pain facilitory systems is enhanced. At the level of the spinal cord {dollar}\\beta{dollar}-endorphin's pain facilitory effect is at least partially dependent upon cholecystokinin, since the intrathecal application of CCK receptor antagonists enhanced {dollar}\\beta{dollar}-endorphin induce antinociception. However, CCK may not be exclusive and other neurotransmitters may also be involved in the expression of opioid induced pain facilitation. A more thorough understanding of these complex neuronal pain modulatory systems and the influence of stress upon them, may potentially lead to the development of more effective therapeutic agents to aid in pain management.