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

Neuromodulation : Journal of the International Neuromodulation Society
Shinichi KokubuTony L Yaksh

Abstract

DMT-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. Adult 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. 1) 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 fo...Continue Reading

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Citations

May 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria DumitrascutaMariana Spetea
Nov 27, 2020·Journal of Neuroinflammation·Huaping XuLinbo Shi
Apr 9, 2021·Peptides·Richard J Bodnar
May 7, 2021·Journal of Medicinal Chemistry·Samuel ObengChristopher R McCurdy

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