Abstract
LIT-002, A HIGHLY POTENT AND SELECTIVE NON-PEPTIDE OXYTOCIN RECEPTOR AGONIST FOR DURABLE RELIEF OF NEUROPATHIC PAIN
Mélanie Kremerand 11 co-authors
Centre National de la Recherche Scientifique, Université de Strasbourg
FENS Forum 2026 (2026)
Barcelona, Spain
Presenter and authors
Presenter
Mélanie Kremer
Centre National de la Recherche Scientifique, Université de Strasbourg
Co-authors
Noémie Willem; Aurélia Cès; Sarah Jester; Henrico-Pio Basile; Juliette Kaeffer; Alexandre Charlet; Ipek Yalcin; Yohann Bohren; Sébastien Cagnol; Stephane Mery; Marcel Hibert
Abstract
Background: Neuropathic pain is difficult to treat and current first-line therapies often provide insufficient relief and induce dose-limiting side effects. Oxytocin signaling has emerged as a promising target for pain modulation, but clinical translation has been limited by the poor pharmacokinetics of peptide agonists.
Methods: We investigated the analgesic efficacy of LIT-002, a highly potent and selective non-peptide oxytocin receptor agonist, in mouse models of neuropathic pain. Mechanical, cold, and heat hypersensitivity were assessed in the sciatic nerve cuff model and in a chemotherapy-induced neuropathic pain model. LIT-002 was administered acutely or chronically via intraperitoneal injection or voluntary oral intake. Spontaneous pain and locomotor activity were also evaluated. Pharmacological antagonism was used to identify the site of action and confirm oxytocin receptor specificity.
Results: LIT-002 produced a robust and dose-dependent attenuation of mechanical hypersensitivity following acute administration. Repeated intraperitoneal or oral treatment induced a complete and sustained reversal of mechanical and cold hypersensitivity, comparable to pregabalin, and restored normal weight-bearing on the injured paw. LIT-002 did not affect spontaneous locomotor activity, indicating the absence of sedative effects. The antihypersensitivity effect of LIT-002 was abolished by a brain-penetrant oxytocin receptor antagonist but not by a peripherally restricted antagonist, demonstrating LIT-002 specificity to oxytocin receptor and a central oxytocin receptor-dependent mechanism. LIT-002 also significantly reduced mechanical, cold, and heat hypersensitivity in chemotherapy-induced neuropathic pain.
Conclusion: These results identify LIT-002 as a promising orally active analgesic candidate providing durable relief of neuropathic pain through central oxytocinergic mechanisms.
Methods: We investigated the analgesic efficacy of LIT-002, a highly potent and selective non-peptide oxytocin receptor agonist, in mouse models of neuropathic pain. Mechanical, cold, and heat hypersensitivity were assessed in the sciatic nerve cuff model and in a chemotherapy-induced neuropathic pain model. LIT-002 was administered acutely or chronically via intraperitoneal injection or voluntary oral intake. Spontaneous pain and locomotor activity were also evaluated. Pharmacological antagonism was used to identify the site of action and confirm oxytocin receptor specificity.
Results: LIT-002 produced a robust and dose-dependent attenuation of mechanical hypersensitivity following acute administration. Repeated intraperitoneal or oral treatment induced a complete and sustained reversal of mechanical and cold hypersensitivity, comparable to pregabalin, and restored normal weight-bearing on the injured paw. LIT-002 did not affect spontaneous locomotor activity, indicating the absence of sedative effects. The antihypersensitivity effect of LIT-002 was abolished by a brain-penetrant oxytocin receptor antagonist but not by a peripherally restricted antagonist, demonstrating LIT-002 specificity to oxytocin receptor and a central oxytocin receptor-dependent mechanism. LIT-002 also significantly reduced mechanical, cold, and heat hypersensitivity in chemotherapy-induced neuropathic pain.
Conclusion: These results identify LIT-002 as a promising orally active analgesic candidate providing durable relief of neuropathic pain through central oxytocinergic mechanisms.