• Alain Van Elstraete, Philippe Sitbon, Leila Hamdi, Victor Juarez-Perez, Jean-Xavier Mazoit, Dan Benhamou, and Catherine Rougeot.
• From the Laboratoire d'Anesthésie, U1195-Inserm, Université Paris-Sud and Université Paris-Saclay, Le Kremlin Bicêtre, Le Kremlin Bicêtre, France.
• Anesth. Analg. 2018 Jun 1; 126 (6): 2102-2111.

BackgroundNeuropathic 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.MethodsIn 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.ResultsHere, 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.ConclusionsThese observations suggested that STR-324 may be an effective addition to the multimodal approach for treating clinical neuropathic pain.

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