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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Specific enhancement by fentanyl of the effects of intrathecal bupivacaine on nociceptive afferent but not on sympathetic efferent pathways in dogs.

BACKGROUND: Bupivacaine alone, or in combination with opioids, has been shown to provide adequate pain relief without motor paralysis. This study examined the effects of bupivacaine administered intrathecally on sympathetic efferent and A delta- and C-fiber-mediated afferent pathways in dogs and the interactions with intrathecal fentanyl. METHODS: Spontaneous activity in renal sympathetic nerves was observed, as were reflex somatosympathetic responses mediated by A delta and C fibers evoked by supramaximal electrical stimulation of the tibial and radial nerve. Bupivacaine was administered intrathecally in doses of 0.5, 1, 2, and 3.5 mg, each in 0.5 ml, and 7 mg in 1 ml with or without pretreatment with 5.4 mg intrathecal fentanyl (ED25 for depression of C tibial reflexes) in each of five preparations. RESULTS: Bupivacaine caused a dose-dependent inhibition of both A delta- and C-fiber-mediated somatosympathetic responses evoked by tibial nerve stimulation. The depression of radial and tibial nerve reflexes and spontaneous renal sympathetic activity was similar. Pretreatment with fentanyl (5.4 micrograms, intrathecally) depressed tibial C-fiber reflexes by only 23.8% without any significant effect on either tibial A delta or radial A delta and C fiber responses. Fentanyl markedly enhanced the effect of subsequent doses of bupivacaine on tibial A delta and C reflexes without any additional effect on either spontaneous sympathetic activity or radial responses. CONCLUSIONS: Intrathecal bupivacaine has no selectivity for the afferent and efferent pathways, and intrathecal fentanyl acts synergistically to enhance the effect of bupivacaine on the afferent pathway without a measurable effect on sympathetic outflow.[1]


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