Baclofen inhibits more effectively C-afferent than Adelta-afferent glutamatergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices

T Ataka, E Kumamoto, K Shimoji, M Yoshimura
Pain 2000, 86 (3): 273-82
Although intrathecal administration of baclofen, a selective GABA(B)-receptor agonist, is known to have an antinociceptive effect on various pain models, the role of presynaptic GABA(B) receptors in antinociception is not well characterized. In the present study, the action of baclofen on primary afferent-evoked glutamatergic excitatory transmission was examined in substantia gelatinosa (SG) neurons of an adult rat spinal cord slice with an attached dorsal root, prepared from the lumbar segment, by use of the blind whole-cell patch-clamp technique. Under the condition where a postsynaptic action of baclofen was inhibited, baclofen (1 microM) reduced the amplitudes of excitatory postsynaptic currents (EPSCs; V(H)=-70 mV) which were monosynaptically evoked by stimulating primary-afferent C- and/or Adelta-fibers and which were remarkably depressed by CNQX (10 microM). The identification of the C-fiber or Adelta-fiber EPSC was based on antidromic action potentials recorded from neurons of isolated dorsal root ganglia. The C-fiber EPSC was depressed in peak amplitude by baclofen (1 microM) to a larger extent than the Adelta-fiber EPSC (20 and 45% of control, respectively). Each of the baclofen actions was suppressed by a selective GABA(B)-receptor antagonist, CGP 35348 (50 microM). Baclofen (1 microM) did not affect a response of SG neurons to bath-applied AMPA (10 microM). These results indicate that baclofen inhibits the release of L-glutamate from Adelta and C primary-afferent terminals in the SG through the activation of GABA(B) receptor; this action is more effective to C-fiber than Adelta-fiber transmission. Considering that the SG is the main part of termination of Adelta- and C-fibers transmitting nociceptive information, the present finding would account for at least a part of the inhibitory action of baclofen on pain transmission.

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