The Opiorphin Analog STR-324 Decreases Sensory Hypersensitivity in a Rat Model of Neuropathic Pain.

Abstract

BACKGROUND:

Neuropathic pain represents a therapeutic challenge, and treatments with increased efficacy and tolerability still need to be developed. Opiorphin protects endogenous enkephalins from degradation, potentiating enkephalin-dependent analgesia via the activation of opioid pathways. Enkephalins are natural ligands of opioid receptors, with strong affinity for δ-opioid receptors. Expression of functional δ-opioid receptors increases in sensory neurons after peripheral nerve injury in neuropathic pain models. In a postoperative pain model, opiorphin and its stable analog STR-324 have an analgesic potency comparable to that of morphine, but without adverse opioid-related side effects. Consequently, administration of endogenous opiorphin peptides or STR-324 might be effective in managing peripheral neuropathic pain.

METHODS:

In this study, STR-324 was administered intravenously over the course of 7 days to rats with mononeuropathy induced by L5-L6 spinal nerve root ligation. The rats exhibited mechanical allodynia, thermal hyperalgesia, and spontaneous pain-related behavior throughout the testing period.

RESULTS:

Here, we report that the continuous administration of STR-324 significantly reduced mechanical allodynia and spontaneous pain-related behavior from day 2 to day 7 in animals that received 10 or 50 µg/h of STR-324 as compared to placebo-treated animals (P < .00001 and P < .0011, respectively, for mechanical allodynia; P = .028 and P = .0049, respectively, for spontaneous pain-related behavior). In addition, STR-324 reduced the pain-evoked expression of spinal c-Fos in this model, demonstrating that it acts at least in part through inhibition of endogenous nociceptive pathways.

CONCLUSIONS:

These observations suggested that STR-324 may be an effective addition to the multimodal approach for treating clinical neuropathic pain.

• Authors: Alain Van Elstraete, Philippe Sitbon, Leila Hamdi, Victor Juarez-Perez, Jean-Xavier Mazoit, Dan Benhamou, Catherine Rougeot
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 126 Issue 6 Pg. 2102-2111 (06 2018) ISSN: 1526-7598 [Electronic] United States
• PMID: 28806211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oligopeptides
• Salivary Proteins and Peptides
• glutaminyl-arginyl-phenylalanyl-seryl-arginine

Topics

• Administration, Intravenous
• Animals
• Disease Models, Animal
• Hyperalgesia (drug therapy, metabolism, pathology)
• Male
• Neuralgia (drug therapy, metabolism, pathology)
• Oligopeptides (administration & dosage, chemistry)
• Pain Measurement (drug effects, methods)
• Rats
• Rats, Sprague-Dawley
• Salivary Proteins and Peptides (administration & dosage, chemistry)