The combined effects of N-type calcium channel blockers and morphine on A delta versus C fiber mediated nociception
| Autor: | Charles E. Laurito, David C. Yeomans, Vesna Pirec, Ying Lu |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
chemistry.chemical_element
Calcium N-type calcium channel Pharmacology Nerve Fibers Myelinated Rats Sprague-Dawley Calcium Channels N-Type Nerve Fibers Postsynaptic potential omega-Conotoxin GVIA Medicine Animals Injections Spinal Pain Measurement Voltage-dependent calcium channel Dose-Response Relationship Drug Morphine business.industry Calcium channel Nociceptors Drug Synergism Calcium Channel Blockers Rats Anesthesiology and Pain Medicine Nociception chemistry Nociceptor μ-opioid receptor business |
| Zdroj: | Anesthesia and analgesia. 92(1) |
| ISSN: | 0003-2999 |
| Popis: | UNLABELLED Intrathecal mu opiates produce analgesia presynaptically by inhibiting calcium ion influx and postsynaptically by increasing potassium flux. Mu receptors are expressed on presynaptic terminals of unmyelinated (C), but not myelinated (A delta) nociceptors. Thus, mu-opioids such as morphine may act presynaptically to inhibit C, but not A delta, neurotransmission, and postsynaptically on dorsal horn cells that receive input from A delta and/or C fiber nociceptors. N-type calcium ion channel blockers, such as omega-conotoxin GVIA (omega-CTX), produce analgesia by impeding flux of calcium ions into A delta and C fiber nociceptor terminals. Thus, morphine and omega-CTX attenuated C fiber nociception additively, possibly indicating the same presynaptic site of action. Conversely, morphine and omega- CTX were supraadditively analgesic on an A delta test, indicating that these agents probably have different sites of action. We conclude that although intrathecal application of either morphine or omega-CTX attenuates both A delta and C fiber mediated nociception in rats, the combined effects are quite different for the two fiber types. Specifically, although coadministration of morphine with omega-CTX produces an additive, apparently presynaptic antinociception for C fiber-mediated responses, the combination produces a clearly supraadditive, and likely synergistic effect on A delta mediated nociception, probably by acting at pre and postsynaptic sites, respectively. IMPLICATIONS This study demonstrates that combined spinal administration of mu opioids and N-type calcium channel blockers may be useful in providing analgesia for A delta mediated (first, sharp) pain while minimizing the side effects of both drugs. |
| Databáze: | OpenAIRE |
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