Evidence for central opioid receptors in the immunomodulatory effects of morphine: review of potential mechanism(s) of action

This review will discuss studies demonstrating that activation of opioid receptors within the central nervous system alters various immune system parameters. Specifically, natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogen appear to be modulated predominantly, if not exclusively, through central opioid receptors. The potential mechanisms by which central opioid receptors appear to modulate these peripheral immune functions will be examined by evaluating the role of both the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system. The studies discussed below indicate that acute administration of morphine or related compounds appears to primarily alter peripheral immune function through the sympathetic nervous system, while more prolonged exposure to opioids alter the immune system predominantly by activation of the HPA axis. Finally, the potential clinical relevance of these observations are discussed in relationship to both the therapeutic use, as well as the abuse of opioid compounds.