Local application of morphine suppresses glutamate-evoked activities of C and Aδ afferent fibers in rat hairy skin

Behavior studies have demonstrated that local application of morphine in peripheral tissues resulted in a significant antinociceptive effect, but there has been no electrophysiological evidence to support the peripheral mechanism of opioid antinociception. The purpose of the present study was to investigate whether local application of morphine suppressed the glutamate-evoked activities of C and Aδ primary afferent fibers in dorsal hairy skin of rat in vivo. The single unit activities of the C and Aδ afferent fibers were recorded by means of isolation of the fiber filaments from the dorsal cutaneous nerve branches, and the effects of glutamate and glutamate plus morphine injected into the receptive field on these activities were determined. The results revealed that most of the C and Aδ fibers were excited significantly by local injection of glutamate (0.3 mM), with the percentage being 81% (22/27, for C fibers) and 73% (36/49, for Aδ fibers), respectively. The glutamate-induced excitatory response was significantly suppressed by co-injection of morphine (1.0 mM). The mean discharge rates of C fibers and Aδ fibers decreased from 28.96 ± 6.85, 28.99 ± 3.79 impulses/min to 4.40 ± 1.76, 2.72 ± 0.71 impulses/min, respectively. The suppressing effect of morphine was reversed by pretreatment with opioid receptor antagonist naloxone (1.0 mM). These findings suggest that local application of morphine can suppress the glutamate-evoked activities of the fine fibers in rat hairy skin and thus provide an electrophysiological evidence for peripheral antinociception of opioids.