Endogenous Opioid Peptides Acting at æ-Opioid Receptors in the Dorsal Horn
Contribute to Midbrain Modulation of Spinal Nociceptive Neurons.
Denes Budai, Ph.D., Howard L. Fields, M.D., Ph.D..
Departments of Neurology and Physiology and the W.M. Keck Foundation Center
for Integrative Neuroscience, University of California, San Francisco, 94143-
0114.
APStracts 4:297N, 1997.
ABSTRACT
Activation of neurons in the midbrain periaqueductal gray (PAG) inhibits
spinal dorsal horn neurons and produces behavioral antinociception in animals
and analgesia in humans. Although dorsal horn regions modulated by PAG
activation contain all three opioid receptor classes (æ, ë and k), as well as
enkephalinergic interneurons and terminal fields, descending opioid-mediated
inhibition of dorsal horn neurons has not been demonstrated. We examined the
contribution of dorsal horn æ-opioid receptors to the PAG-elicited descending
modulation of nociceptive transmission. Single unit extracellular recordings
were made from rat sacral dorsal horn neurons activated by noxious heating of
the tail. Microinjections of bicuculline (BIC ) in the ventrolateral PAG led
to a 60-80% decrease in the neuronal responses to heat. At the same time, the
responses of the same neurons to iontophoretically applied NMDA or kainic acid
were not consistently inhibited. The inhibition of heat-evoked responses by
PAG BIC was reversed by iontophoretic application of the selective æ-opioid
receptor antagonists, CTOP and CTAP. A similar effect was produced by
naloxone, however, naloxone had an excitatory influence on dorsal horn neurons
in the absence of PAG-evoked descending inhibition. This is the first
demonstration that endogenous opioids acting via spinal æ-opioid receptors
contribute to brainstem control of nociceptive spinal dorsal horn neurons. The
inhibition appears to result in part from presynaptic inhibition of afferents
to dorsal horn neurons.
Received 8 August 1996; accepted in final form 21 October 1997.
APS Manuscript Number J650-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 29 October 1997