Teleantagonism: A pharmacodynamic property of the primary nociceptive neuron
| Autor: | Fernando Q. Cunha, Djane Braz Duarte, B B Lorenzetti, Mani Indiana Funez, Sérgio H. Ferreira, Carlos Amílcar Parada, Luiz F. Ferrari, Daniela Sachs |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Pyrrolidines Sensory Receptor Cells Dopamine Narcotic Antagonists Indomethacin Interleukin-1beta Pain (+)-Naloxone Pharmacology Nitric Oxide Dinoprostone Dorsal root ganglion Quinoxalines medicine Animals Drug Interactions Enzyme Inhibitors Rats Wistar Sensitization Oxadiazoles Multidisciplinary omega-N-Methylarginine Morphine Chemistry Naloxone Anti-Inflammatory Agents Non-Steroidal Nociceptors Biological Sciences Rats Analgesics Opioid medicine.anatomical_structure Opioid Hyperalgesia Nociceptor Omega-N-Methylarginine NMDA receptor medicine.symptom medicine.drug Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 105(49) |
| ISSN: | 1091-6490 |
| Popis: | Previous work from our group showed that intrathecal (i.t.) administration of substances such as glutamate, NMDA, or PGE 2 induced sensitization of the primary nociceptive neuron (PNN hypernociception) that was inhibited by a distal intraplantar (i.pl.) injection of either morphine or dipyrone. This pharmacodynamic phenomenon is referred to in the present work as “teleantagonism”. We previously observed that the antinociceptive effect of i.t. morphine could be blocked by injecting inhibitors of the NO signaling pathway in the paw (i.pl.), and this effect was used to explain the mechanism of opioid-induced peripheral analgesia by i.t. administration. The objective of the present investigation was to determine whether this teleantagonism phenomenon was specific to this biochemical pathway (NO) or was a general property of the PNNs. Teleantagonism was investigated by administering test substances to the two ends of the PNN (i.e., to distal and proximal terminals; i.pl. plus i.t. or i.t. plus i.pl. injections). We found teleantagonism when: ( i ) inhibitors of the NO signaling pathway were injected distally during the antinociception induced by opioid agonists; ( ii ) a nonselective COX inhibitor was tested against PNN sensitization by IL-1β; ( iii ) selective opioid-receptor antagonists tested against antinociception induced by corresponding selective agonists. Although the dorsal root ganglion seems to be an important site for drug interactions, the teleantagonism phenomenon suggests that, in PNNs, a local sensitization spreads to the entire cell and constitutes an intriguing and not yet completely understood pharmacodynamic property of this group of neurons. |
| Databáze: | OpenAIRE |
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