Premium
Intrathecal antinociceptive interaction between the NMDA antagonist ketamine and the opioids, morphine and biphalin
Author(s) -
Kosson Dariusz,
Klinowiecka Anna,
Kosson Piotr,
Bonney Iwona,
Carr Daniel B.,
MayznerZawadzka Ewa,
Lipkowski Andrzej W.
Publication year - 2008
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2007.10.005
Subject(s) - morphine , ketamine , nmda receptor , analgesic , pharmacology , nociception , opioid , antagonist , medicine , anesthesia , receptor
Biphalin is an opioid peptide analogue that currently is under clinical development as a new type of site‐directed analgesic. In rats, the intrathecal (i.t.) analgesic potency of biphalin is 1000‐fold greater than morphine. Such a high activity may reflect this compound's activation of three types of opioid receptors (μ, δ and κ). NMDA receptors also play an important role in nociceptive processing. Therefore, we investigated in rats whether an NMDA antagonist may influence biphalin‐induced antinociception. In the present study, ketamine was chosen because of the widespread safe use of this drug in clinical practice. I.t. application of ketamine alone had relatively little analgesic effect and its excitatory effects limited possible doses of the drug. Co‐administration of ketamine with biphalin or morphine produced markedly greater antinociception than biphalin or morphine alone in acute, thermal tail flick testing. These results suggest that NMDA antagonists may be useful potentiators of biphalin analgesia. Thus, to obtain the same spinal antinociceptive effect, lower doses of biphalin or morphine are required when ketamine is co‐administered.