Mu and delta opioid receptor-like immunoreactivity in the cervical spinal cord of the rat after dorsal rhizotomy or neonatal capsaicin: an analysis of pre- and postsynaptic receptor distributions.
Opioid compounds have powerful analgesic properties when administered to the spinal cord. These effects are exerted through mu and delta opioid receptors, and both pre- and postsynaptic mechanisms have been implicated. To specifically address the relative pre- and postsynaptic contribution to spinal opioid analgesia, we have quantitatively assessed the pre- vs. postsynaptic distribution of the mu-opioid (MOR-1, MOP(1)) and delta-opioid receptors (DOR-1, DOP(1)). We also examined the rostro-caudal arborization of MOR-1 and DOR-1 immunoreactive primary sensory neurons, using an isolated dorsal root preparation. These results were compared to those obtained by labeling for calcitonin gene-related peptide (CGRP), a neuropeptide whose expression in the spinal cord is restricted to the terminals of small diameter primary sensory neurons. We estimate that approximately one half of MOR-1 and two thirds of DOR-1 immunoreactivity in the cervical spinal cord is located on primary afferent fibers. These fibers have a broad rostro-caudal distribution, extending at least three segments rostral and caudal to their segment of entry. Regardless of marker used, the rostral projection was greatest, however, the distribution of CGRP-immunoreactive fibers differed somewhat in that they had a much smaller projection to the most caudal segments examined. Our results suggest that presynaptic delta opioid actions predominate, but that there are mixed pre- and postsynaptic inhibitory effects exerted by opioid analgesics that act at the spinal cord mu opioid receptor.
Abbadie
Catherine
C
Department of Anatomy, W.M. Keck Foundation Center for Integrative Neuroscience, University of California-San Francisco, San Francisco, CA 94143, USA.
Lombard
Marie Christine
MC
Besson
Jean Marie
JM
Trafton
Jodie A
JA
Basbaum
Allan I
AI
D000818:Animals; D000831:Animals, Newborn; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000187:drug effects; D019051:Rhizotomy; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013126:Spinal Nerve Roots / Q000378:metabolism
D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D017661:Receptors, Presynaptic; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin