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Endogenous morphine: A role in wellness medicine

George B. Stefano

Med Sci Monit 2004; 10(6): ED5-5

ID: 16400

The demonstration of the multiplicity of opiate receptor types has led to the understanding that,
depending on their site of action, opioid peptides as well as opiate alkaloids may bind to more than one opiate receptor subtype. In addition to the two main µ opiate receptor subtypes, µ1 and µ2, our laboratory has demonstrated a third µ opiate receptor (µ3) that is selective for opiate alkaloids but insensitive to opioid peptides. Recently, the µ3 opiate receptor subtype has been cloned from human immune, vascular and neural tissues. This µ3 story complements many biochemical reports; demonstrating morphine is an endogenous signaling molecule, functioning in the
capacity of a neurotransmitter and hormone. Adding additional evidence to this hypothesis are the fi ndings of morphine precursors in mammalian and invertebrate tissues. The reports published in this issue of MSM complement this story while advancing the hypothesis by placing opiate alkaloid signaling in limbic structures. The pharmacological characteristics of exogenous morphine fi nd a role for explaining morphine action in an “emotional” and belief setting. Within this context, multiple component expectation-induced placebo effects may involve morphinergic signaling, since a reduction of placebo effects by the opioid selective antagonist naloxone has been demonstrated. Neurons immunoreactive for morphine are largely present all along the extension of PAG and in brainstem raphe nuclei. This process also may be active in altering the experience of pain. Moreover, the prefrontal cortex possesses close neural connections to limbic
components such as the hippocampal formation and cingulate cortex where morphine immunoreactivity
is largely present in neurons and fi bers. These limbic areas play a major role in memory
processes and also mediate motivational, affective and autonomic responses often accompanying
pain. Additionally, endogenous morphine appears to modulate memory processes playing a role in weakening the memory of a nociceptive experience. Limbic areas also are connected to the prefrontal cortex, which integrates emotion, memory, belief, expectation, motivation and reward processing, i.e, affective and motivational responses. Taken together, prefrontal cortex activation in placebo as well as complementary medical techniques (CMT) may refl ect a form of externally elicited top-down CNS control, possibly involving morphinergic pathways. Common brain structures like frontal and limbic regions get activated in various CMT approaches, indicating a crucial role of affect and belief. CMT therapies also possess a stress-reducing capacity that may be addressed in self-care-oriented medical procedures, some of them accepted for their low-cost (although effective) way of acting in the healing process given their down regulating properties. While medical knowledge and technical abilities are expanding, they still have to be affordable. CMT may help to solve this problem. Thus, the existence of subjective CNS phenomena and commonalities in CMT may emphasize the signifi cance of naturally occurring health processes
and general self-care capabilities. Trust and belief may increasingly become part of future therapeutic
strategies and regular medicine.

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