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Letters to Nature
Nature 265, 358 - 360 (27 January 1977); doi:10.1038/265358a0

Stress-induced parallel changes in central opioid levels and pain responsiveness in the rat

J. MADDEN IV, H. AKIL, R. L. PATRICK & J. D. BARCHAS

Nancy Pritzker Laboratory of Behavioral Neurochemistry, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305

THE isolation and identification of endogenous opiate-like peptides from mammalian brain1,2, and from pituitary3–5 has led to an active investigation of their pharmacological properties. These peptides—the enkephalins and endorphins—have been shown to produce naloxone-reversible analgesia6,7, tolerance, and withdrawal7. While these effects seem consonant with those of morphine and other exogenous narcotics, little is yet known about the intrinsic, physiological functions of the opioid peptides. Since powerful analgesia is a prominent and reliable phenomenon associated with the administration of both narcotic alkaloids and brain opioid peptides, it seems reasonable to suggest that the opioid peptides may normally function to modulate pain responsiveness. Furthermore, work with stimulation-produced analgesia has suggested the existence, in mammalian brain, of a pain-inhibitory system with an opiate-like link8,9. We have, therefore, hypothesised that such an endogenous system may be engaged by either environmental, sensory, or other physiological events which lead to adaptive changes in pain responsiveness. For example, noxious or stressful stimuli may recruit pain-inhibitory mechanisms in the central nervous system, bringing about alterations in enkephalins and endorphins, with concurrent or subsequent changes in responses to pain. Consistent with this hypothesis, we now report that inescapable acute stress causes a significant increase in levels of opioid peptides with a concurrent decrease in pain responsiveness in the rat. Furthermore, both the biochemical and behavioural changes are “reversed” by repeated exposure to stress. A preliminary report of this work has been made10.

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References

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