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PAIN MEDICINE

Functional Magnetic Resonance Imaging Measures of the Effects of Morphine on Central Nervous System Circuitry in Opioid-Naive Healthy Volunteers

Lino Becerra, PhD^*, Kim Harter, BA, R. Gilberto Gonzalez, MD, PhD, and David Borsook, MD, PhD^*

From the *P.A.I.N. Group, Brain Imaging Center; Department of Psychiatry, McLean Hospital; and Departments of Radiology and Neuroradiology, Massachusetts General Hospital – Athinoula Martinos Biomedical Imaging Center, and Harvard Medical School, Boston, Massachusetts.

Address correspondence and reprint requests to David Borsook, MD, PhD, P.A.I.N. Group, Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478. Address e-mail to dborsook{at}mclean.harvard.edu.

In this pilot study, we used functional magnetic resonance imaging (fMRI) to study the effects of morphine in 8 healthy, opioid-naïve volunteers. Intravenous small-dose morphine (4 mg/70 kg) or saline was administered to volunteers undergoing a fMRI scan. Infusion of morphine, but not saline, elicited mild euphoria without aversive symptoms and resulted in positive signal changes in reward structures including the nucleus accumbens, sublenticular extended amygdala, orbitofrontal cortex, and hippocampus. The positive signal in the accumbens was opposite to the signal previously reported for noxious stimuli. Morphine produces a decreased signal in cortical areas in a similar manner to sedative-hypnotic drugs such as propofol or midazolam. Activation in endogenous analgesic regions was observed in the periaqueductal gray, the anterior cingulate gyrus (decreased signal), and hypothalamus (increased signals). The pattern of activation in reward circuitry was similar to that reported for euphoric drugs of abuse, providing a model to evaluate the initial effects of morphine on the central nervous system components of the circuitry involved in addiction. The segregation of fMRI response that was observed in cortical versus subcortical regions suggests a dissociation of reward from sensory-motor and cognitive functions. Activation patterns were opposite to those previously observed for the µ antagonist, naloxone.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999