The Opiorphin Analog STR-324 Decreases Sensory Hypersensitivity in a Rat Model of Neuropathic Pain. (June 2018)

• Record Type: Journal Article
• Authors: Van Elstraete, Alain; Sitbon, Philippe; Hamdi, Leila; Juarez-Perez, Victor; Mazoit, Jean-Xavier; Benhamou, Dan; Rougeot, Catherine
• Is Part Of: Anesthesia & analgesia. Volume 126:Number 6(2018)
• Publication Date: 2018-06
• Subjects: Anesthesiology -- Periodicals; Anesthesia; Anesthesiology; Analgesia; Analgesics; Anesthesiology -- Periodicals; 617.9605
• DOI: 10.1213/ANE.0000000000002413
• Languages: English
• ISSNs: 0003-2999

Abstract

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.