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

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 Adelta- and C-afferent responses.

METHODS: Using the whole cell patch clamp technique, the authors investigated the presynaptic inhibitory actions of micro-, delta-, and kappa-opioid receptor agonists on primary afferent-evoked excitatory postsynaptic currents (EPSCs) in substantia gelatinosa neurons of adult rat spinal cord slices.

RESULTS: The micro agonist DAMGO (0.1, 1 microM) reduced the amplitude of glutamatergic monosynaptic Adelta- or C fiber-evoked EPSCs. C fiber-evoked EPSCs were inhibited to a greater extent than Adelta fiber-evoked EPSCs. The delta agonist DPDPE (1, 10 microM) produced modest inhibition of Adelta- or C fiber-evoked EPSCs. In contrast, the kappa agonist U69593 (1 microM) did not affect the amplitude of either Adelta or C fiber-evoked EPSCs.

CONCLUSIONS: These results indicate that opioids suppress excitatory synaptic transmission mainly through activation of micro receptors on primary afferent C fibers. Given that the substantia gelatinosa is the main termination of Adelta and C fibers transmitting nociceptive information, the current findings may partially explain the different potency of opioid agonists.