93: Topical ziconotide as a safe strategy to relieve pain at the periphery

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Developing methodology/technology, Pharmacological interventions, Drug development

Background and Aims: Ziconotide (PRIALT) is a calcium channel blocker isolated from cone snail venom and approved for the treatment of severe and resistant chronic pain. It acts centrally by blocking presynaptic Cav2.2 channels in the dorsal horns of the spinal cord, reducing neurotransmitter release and spinal pain transmission. Because of its central mechanism of action and peptidic nature, it must be delivered intrathecally. However, this route of administration and the numerous central adverse effects it induces make ziconotide a last resort option. We found that peripheral ziconotide is analgesic and that its topical application relieves pain while avoiding central toxicity.

Methods: The peripheral effect of ziconotide on sensory neurons excitability was studied using mouse cultured sensory neurons (calcium imaging) and skin-nerve preparations (electrophysiology). In vivo, different routes of administration of ziconotide where compared, ultimately leading us to prepare a topical formulation of ziconotide by mixing the drug with a commercially available lipocream (Excipial). This formulation was tested at different concentrations in inflammatory pain models (capsaicin, carrageenan and post-operative pain) and in a neuropathic pain model (spinal nerve ligation) while central toxicity was evaluated through motor strength and coordination.

Results: Ziconotide decreases the hyperexcitability of sensory neurons exposed to an inflammatory cocktail in vitro (cultured sensory neurons) and ex vivo (skin-nerve recordings). In vivo, intraplantar ziconotide is analgesic and does not induce motor adverse effects, unlike intrathecal injection. Topical application of ziconotide is effective in relieving inflammatory pain and, to a lesser extent, neuropathic pain. No motor deficit was observed in animals, even at doses 100 times higher than the analgesic dose in inflammatory models.

Conclusions: Ziconotide appears to be effective for relieving pain at the periphery, and its central toxicity can be avoided using topical administration. This simple topical reformulation could enable rapid clinical translation and may extend its therapeutic use, providing new options for patients suffering from chronic pain.

References: .

Presenting Author: Stéphane Lolignier
Submitting Author: Stéphane Lolignier

Senior Author: Stéphane Lolignier

IASP 2026 Global Year theme of Neuropathic Pain: No

• Julien Schopp: B.Sc. - Domiconus
• Mathilde Schneider: Pharm.D. - Domiconus
• Yaiza Arnaiz Alcacer: M.Sc. - Domiconus
• Romane Bony: M.Sc. - NEURODOL lab, UMR 1107 INSERM/Université Clermont Auvergne
• Hugo Alendouro: M.Sc. - NEURODOL lab, UMR 1107 INSERM/Université Clermont Auvergne
• Maxence Maugis: B.Sc. - NEURODOL lab, UMR 1107 INSERM/Université Clermont Auvergne
• Mathieu Meleine: Ph.D. - NEURODOL lab, UMR 1107 INSERM/Université Clermont Auvergne
• Julie Barbier: B.Sc. - NEURODOL lab, UMR 1107 INSERM/Université Clermont Auvergne
• Emmanuelle Lainé: Ph.D. - NEURODOL lab, UMR 1107 INSERM/Université Clermont Auvergne
• Jérôme Busserolles: Ph.D. - NEURODOL lab, UMR 1107 INSERM/Université Clermont Auvergne
• Thomas Suply: Ph.D. - Domiconus
• Stéphane Lolignier: Ph.D. - NEURODOL lab, UMR 1107 INSERM/Université Clermont Auvergne