Differential presynaptic effects of opioid agonists on Aδ- and C-afferent glutamatergic transmission to the spinal dorsal horn

Abstract

BACKGROUND: Although intrathecal administration of opioids produces antinociceptive effects in the spinal cord, it has not been established whether intrathecal opioid application more effectively terminates C fiber-mediated pain than A fiber-mediated pain. Here, the authors focus on the differences in opioid actions on Aδ- and C-afferent responses. METHODS: Using the whole cell patch clamp technique, the authors investigated the presynaptic inhibitory actions of μ-, δ-, and κ-opioid receptor agonists on primary afferent-evoked excitatory postsynaptic currents (EPSCs) in substantia gelatinosa neurons of adult rat spinal cord slices. RESULTS: The μ agonist DAMGO (0.1, 1 μm) reduced the amplitude of glutamatergic monosynaptic Aδ- or C fiber-evoked EPSCs. C fiber-evoked EPSCs were inhibited to a greater extent than Aδ fiber-evoked EPSCs. The δ agonist DPDPE (1, 10 μm) produced modest inhibition of Aδ- or C fiber-evoked EPSCs. In contrast, the κ agonist U69593 (1 μm) did not affect the amplitude of either Aδ or C fiber-evoked EPSCs. CONCLUSIONS: These results indicate that opioids suppress excitatory synaptic transmission mainly through activation of μ receptors on primary afferent C fibers. Given that the substantia gelatinosa is the main termination of Aδ and C fibers transmitting nociceptive information, the current findings may partially explain the different potency of opioid agonists. © 2007 American Society of Anesthesiologists, Inc.