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Superior Analgesic Effect of H‐Dmt‐D‐Arg‐Phe‐Lys‐NH 2 ([Dmt 1 ]DALDA), a Multifunctional Opioid Peptide, Compared to Morphine in a Rat Model of Neuropathic Pain
Author(s) -
Shimoyama Megumi,
Schiller Peter W.,
Shimoyama Naohito,
Toyama Satoshi,
Szeto Hazel H.
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12003
Subject(s) - neuropathic pain , analgesic , pharmacology , morphine , medicine , hyperalgesia , opioid , dermorphin , chemistry , anesthesia , nociception , receptor , opioid peptide
H‐Dmt‐D‐Arg‐Phe‐Lys‐NH 2 ([Dmt 1 ]DALDA) is a synthetic tetrapeptide with extraordinary selectivity for the mu‐opioid receptor and is an extremely potent analgesic. [Dmt 1 ]DALDA is unusual in the way that the greater part of its analgesic potency appears to be produced by its actions in the spinal cord. Furthermore, [Dmt 1 ]DALDA inhibits norepinephrine re‐uptake and is a mitochondria‐targeted antioxidant. Such characteristics may make [Dmt 1 ]DALDA particularly effective against neuropathic pain. The present study was designed to compare the effects of [Dmt 1 ]DALDA and morphine on thermal hyperalgesia in an experimental neuropathic pain model. Neuropathic pain was induced in rats by surgical ligation of the L5 spinal nerve, and thermal pain thresholds were assessed by latencies of paw withdrawal to radiant heat. The increase in paw withdrawal latency was greater after the administration of [Dmt 1 ]DALDA than that of morphine in neuropathic rats at doses that were equianalgesic in naïve animals. We conclude that [Dmt 1 ]DALDA is more effective than morphine against thermal hyperalgesia in this experimental model of neuropathic pain.