Pain Medicine  |   November 2016
STR-324, a Stable Analog of Opiorphin, Causes Analgesia in Postoperative Pain by Activating Endogenous Opioid Receptor–dependent Pathways
Author Notes
  • From the Service d’Anesthésie, Institut Gustave Roussy, Villejuif, France (P.S.); Laboratoire d’Anesthésie, U1195-Inserm, Université Paris-Sud and Université Paris-Saclay, Le Kremlin Bicêtre, France (P.S., A.V.E., L.H., J.-X.M., D.B.); Stragen France, Lyon, France (V.J.-P.); AP-HP, Service d’Anesthésie-Réanimation, Hôpitaux Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, France (J.-X.M., D.B.); and Institut Pasteur, Laboratoire de Pharmacologie de la Douleur, Paris, France (C.R.).
  • Submitted for publication October 3, 2015. Accepted for publication July 27, 2016.
    Submitted for publication October 3, 2015. Accepted for publication July 27, 2016.×
  • Corresponding article on page 841.
    Corresponding article on page 841.×
  • Address correspondence to Dr. Sitbon: Service d’Anesthésie, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France. philippe.sitbon@gustaveroussy.fr. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Basic Science / Pain Medicine
Pain Medicine   |   November 2016
STR-324, a Stable Analog of Opiorphin, Causes Analgesia in Postoperative Pain by Activating Endogenous Opioid Receptor–dependent Pathways
Anesthesiology 11 2016, Vol.125, 1017-1029. doi:10.1097/ALN.0000000000001320
Anesthesiology 11 2016, Vol.125, 1017-1029. doi:10.1097/ALN.0000000000001320
Abstract

Background: Opiorphin is a naturally occurring potent analgesic human peptide. It protects enkephalins from degradation and inhibits pain perception in various acute pain models via activation of endogenous opioid pathways. However, the efficacy of opiorphin continuous infusion and its chemically stable form, STR-324, in postoperative pain is unknown.

Methods: Using the Brennan model of plantar incision–induced hypersensitivity, the authors examined the postsurgical analgesic response to mechanical and thermal stimuli of 7-day continuously intravenously infused drugs (8 to 10 rats per group). Antinociception from opiorphin with reference to morphine and STR-324 was assessed. Spinal c-Fos expression and the involvement of opioid receptor–dependent pathways were investigated. The occurrence of respiratory and hemodynamic adverse effects of opiorphin was also tested.

Results: Intravenous infusion of opiorphin significantly reduced responses to mechanical stimuli from days 1 to 4 post surgical period at 143 to 175-kPa mean ranges compared with 23 to 30-kPa mean ranges for vehicle (P < 0.05). During the 3-day postoperative period, no respiratory rate, oxygen saturation, arterial pressure, or heart rate adverse effects were induced by opiorphin. STR-324 consistently inhibited mechanical and thermal hyperalgesia with similar potency as that of opiorphin. Mechanistic analyses demonstrated that the STR-324 antinociceptive effect was reversed by the opioid antagonist, naloxone. Also, STR-324 significantly reduced the number of pain-evoked spinal cFos-immunoreactive nuclei.

Conclusion: Intravenous infusion of opiorphin and STR-324 produced significant antinociceptive effect in a postoperative pain model. This study demonstrates that STR-324 is effective in postoperative pain management due to its strong antihyperalgesic effects mediated via opioid-dependent antinociceptive pathways. Opiorphin analog should represent a new class of potent and safe analgesics.