Evidence map›Paper›PMID 30794333›Full record

ArticleNeuromodulation : journal of the International Neuromodulation Society2019

Characterization of Analgesic Actions of the Chronic Intrathecal Infusion of H-Dmt-D-Arg-Phe-Lys-NH2 in Rat.

Shinichi Kokubu, Kelly A Eddinger, Shigeki Yamaguchi, Lena Libertad Huerta-Esquivel, Peter W Schiller, Tony L Yaksh

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuromodulation : journal of the International Neuromodulation Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 5 countries.

Shinichi KokubuDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, USA.
Kelly A EddingerDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, USA.
Shigeki YamaguchiDepartment of Anesthesiology, Dokkyo Medical University, Tochigi, Japan.
Lena Libertad Huerta-EsquivelDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, USA.
Peter W SchillerDepartment of Pharmacology and Physiology, University of Montreal, Montreal, Quebec, Canada.
Tony L YakshDepartment of Anesthesiology, University of California San Diego, La Jolla, CA, USA.
University of California, San Diego · USDokkyo Medical University · JPUniversidad Autónoma de Nuevo León · MXUniversité de Montréal · CA

Funding

Characterization of Toxicity with Spinal OpiatesR01DA015353 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YAKSH, TONY L. · 2003 to 2017
$4.4M
AIBP and regulation of neuropathic painR01NS102432 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY, YAKSH, TONY L. · 2017 to 2021
$3.0M
NIDA NIH HHS R01 DA015353NINDS NIH HHS R01 NS102432
6 · The paper itself

Abstract

objectivesDMT-DALDA (H-Dmt-D-Arg-Phe-Lys-NH2; Dmt = 2',6'-dimethyltyrosine) is a selective mu opioid agonist. We sought to characterize efficacy, tolerance, dependence and side-effect profile when given by continuous intrathecal infusion. MATERIALS AND

methodsAdult male Sprague Dawley rats were prepared with chronic intrathecal catheters and osmotic mini-pumps to deliver vehicle (saline), DMT-DALDA or morphine. Hind paw thermal escape latencies were assessed. In addition, effects upon intraplantar formalin-evoked flinching and withdrawal after 14 days of infusion were examined. The flare response after intradermal delivery was examined in the canine model.

results1) Intrathecal infusion of 0.3 to 30 pmol/μL/hour of DMT-DALDA or 37.5 nmol/μL/hour of morphine more than 7 or 14 days resulted in a dose-dependent increase in thermal escape latency. The maximum antinociceptive effect was observed between 1 and 4 days after start of infusion with preserved cornea, blink, placing and stepping. By days 12 to 14, response latencies were below baseline. 2) On days 2 to 4 of DMT-DALDA infusion, the pan opioid receptor antagonist naloxone (Nx), but not the delta-preferring antagonist naltrindole, antagonized the analgesic effects. 3) Assessment of formalin flinching on day 1 following IT DMT-DALDA Infusion showed significant analgesia in phases 1 and 2. On day 6 of infusion there was minimal effect, while on day 13, there was an increase in flinching. 4) On days 7 and 14 of infusion Nx resulted in prominent withdrawal signs indicating dependence and withdrawal. 5) Intradermal morphine and DMT-DALDA both yield a naltrexone-insensitive, cromolyn-sensitive flare in the canine model at similar concentrations.

conclusionsThese data suggest that DMT-DALDA is a potent, spinally active agonist with a propensity to produce tolerance dependence and mast cell degranulation. While it was equiactive to morphine in producing mast cell degranulation, it was >1000 fold more potent in producing analgesia, suggesting a possible lower risk in producing a spinal mass at equianalgesic doses.

Indexed as

Analgesics, OpioidAnimalsDogsInjections, SpinalMaleOligopeptidesPain MeasurementRandom AllocationRatsRats, Sprague-DawleyReceptors, Opioid, muAnalgesics, Opioidarginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamideOligopeptidesReceptors, Opioid, muDependenceDMT1-DALDAformalin flinchingintrathecal infusionmu opioid receptortolerancewithdrawal

Identifiers

PMID30794333
PMCPMC6706328
OpenAlexW2917042847

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.