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 A delta- and C-afferent responses.
Methods: Using the whole cell patch clamp technique, the authors investigated the presynaptic inhibitory actions of mu-, delta-, and K-opioid receptor agonists on primary afferent-evoked excitatory postsynaptic currents (EPSCs) in substantia gelatinosa neurons of adult rat spinal cord slices.
Results: The mu agonist DAMGO (0.1, 1 mu m) reduced the amplitude of glutamatergic monosynaptic A delta- or C fiber-evoked EPSCs. C fiber-evoked EPSCs were inhibited to a greater extent than AS fiber-evoked EPSCs. The 5 agonist DPDPE (1, 10 mu m) produced modest inhibition of A delta- or C fiber-evoked EPSCs. In contrast, the K agonist U69593 (1 mu m) did not affect the amplitude of either A delta or C fiber-evoked EPSCs.
Conclusions: These results indicate that opioids suppress excitatory synaptic transmission mainly through activation of mu receptors on primary afferent C fibers. Given that the substantia gelatinosa is the main termination of A delta and C fibers transmitting nociceptive information, the current findings may partially explain the different potency of opioid agonists.