Opioid control of the in vitro release of calcitonin gene-related peptide from primary afferent fibres projecting in the rat cervical cord

Abstract

In vitro superfusion of slices from the dorsal half of the rat cervical enlargement allowed the measurement of spontaneous, K + (30mM)- and capsaicin (0.5 μM)-evoked release of calcitonin gene-related peptide-like immunoreactive material (CGRPLI). The greater part of this immunoreactive material originated in primary afferent fibres since dorsal rhizotomy from C4 to Th2 (8 days before sacrifice) resulted in a 85–90% decrease in CGRPLI release. CGRPLI outflow which persisted after dorsal rhizotomy could still be enhanced by K +-induced depolarization but was no longer sensitive to the stimulatory effect of 0.5 μM capsaicin. Both delta (DTLET, D-Pen 2-D-Pen 5-enkephalin) and mu (DAGO, PL 017) opioid receptor agonists reduced the K + evoked release of CGRPLI from the dorsal half of the cervical enlargement. Morphine was also inhibitory but the selective K opioid agonist U 69593 was inactive. As expected from the involvement of delta and mu receptors, the selective opioid antagonist ICI 174864 and naloxone prevented the inhibitory effects of DTLET and DAGO, respectively. These data suggest that opioid-induced presynaptic inhibition of CGRP-containing primary afferent fibres may be involved in the analgesic effect of intrathecally injected delta and mu opioid agonists in rats.