The Journal of Neurophysiology Vol. 85 No. 1 January 2001, pp. 280-286
Copyright ©2001 by the American Physiological Society
Circuitry Underlying Antiopioid Actions of Cholecystokinin Within
the Rostral Ventromedial Medulla
M. M.
Heinricher,
S.
McGaraughty, and
V.
Tortorici
Department of Neurological Surgery, Oregon Health Sciences
University, Portland, Oregon 97201
Heinricher, M. M.,
S. McGaraughty, and
V. Tortorici.
Circuitry Underlying Antiopioid Actions of Cholecystokinin Within
the Rostral Ventromedial Medulla. J. Neurophysiol. 85: 280-286, 2001. It is now well established that
the analgesic actions of opioids can be modified by
"anti-analgesic" or "antiopioid" peptides, among them
cholecystokinin (CCK). Although the focus of much recent work concerned
with CCK-opioid interactions has been at the level of the spinal cord,
CCK also acts within the brain to modify opioid analgesia. The aim of
the present study was to characterize the actions of CCK in a brain
region in which the circuitry mediating the analgesic actions of
opioids is relatively well understood, the rostral ventromedial medulla
(RVM). Single-cell recording was combined with local infusion of CCK in
the RVM and systemic administration of morphine in lightly anesthetized
rats. The tail-flick reflex was used as a behavioral index of
nociceptive responsiveness. Two classes of RVM neurons with distinct
responses to opioids have been identified. OFF cells are
activated, indirectly, by morphine and µ-opioid agonists, and there
is strong evidence that this activation is crucial to opioid
antinociception. ON cells, thought to facilitate
nociception, are directly inhibited by opioids. Cells of a third class,
NEUTRAL cells, do not respond to opioids, and whether they
have any role in nociceptive modulation is unknown. CCK microinjected
into the RVM by itself had no effect on tail flick latency or the
firing of any cell class but significantly attenuated opioid activation
of OFF cells and inhibition of the tail flick. Opioid
suppression of ON-cell firing was not significantly altered
by CCK. Thus CCK acting within the RVM attenuates the analgesic effect
of systemically administered morphine by preventing activation of the
putative pain inhibiting output neurons of the RVM, the OFF
cells. CCK thus differs from another antiopioid peptide, orphanin
FQ/nociceptin, which interferes with opioid analgesia by potently
suppressing all OFF-cell firing.
