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  • Title: Bupivacaine inhibits glutamatergic transmission in spinal dorsal horn neurons.
    Author: Furutani K, Ikoma M, Ishii H, Baba H, Kohno T.
    Journal: Anesthesiology; 2010 Jan; 112(1):138-43. PubMed ID: 20032703.
    Abstract:
    BACKGROUND: The local anesthetic bupivacaine is thought not only to block sodium channels but also to interact with various receptors. Here, the authors focus on excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord with respect to its importance for nociceptive processing. METHODS: The effects of bupivacaine on the response to exogenous administration of N-methyl-D-aspartate (NMDA) receptor agonists were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique. RESULTS: Bupivacaine (0.5, 2 mm) dose-dependently reduced the peak amplitudes of exogenous NMDA-induced currents. However, this inhibitory effect of bupivacaine (2 mm) was not blocked by the presence of tetrodotoxin, a sodium channel blocker, or La(3+), a voltage-gated Ca+ channel blocker, and was unaffected by changes in pH conditions. Moreover, intrapipette guanosine-5'-O-(2-thiodiphosphate) (1 mm), a G-protein inhibitor, did not block the reduction of NMDA current amplitudes by bupivacaine. Similarly, lidocaine, ropivacaine, and mepivacaine also reduced the amplitudes of NMDA-induced currents. CONCLUSIONS: These findings raise the possibility that the antinociceptive effect of bupivacaine may be due to direct modulation of NMDA receptors in the superficial dorsal horn. In addition to voltage-gated sodium channels, glutamate NMDA receptors are also important for analgesia induced by local anesthetics.
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