Teleantagonism: A pharmacodynamic property of the primary nociceptive neuron.
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-1beta; (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.
Funez
Mani I
MI
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049-900, São Paulo, Brazil.
Ferrari
Luiz F
LF
Duarte
Djane B
DB
Sachs
Daniela
D
Cunha
Fernando Q
FQ
Lorenzetti
Berenice B
BB
Parada
Carlos A
CA
Ferreira
Sérgio H
SH
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D009292:Narcotic Antagonists; D010069:Oxadiazoles; D011759:Pyrrolidines; D011810:Quinoxalines; C060223:ICI 204448; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009270:Naloxone; D009020:Morphine; D015232:Dinoprostone; D004298:Dopamine; D007213:Indomethacin
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