Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent analgesic activity, and light-induced activation of one of these compounds (JF-NP-26) in the thalamus was found to induce analgesia in models of inflammatory and neuropathic pain. We used an established mouse model of BTcP based on the injection of cancer cells into the femur, followed, 16 days later, by systemic administration of morphine. BTcP was induced by injection of endothelin-1 (ET-1) into the tumor, 20 min after morphine administration. Mice were implanted with optic fibers delivering light in the visible spectrum (405 nm) in the thalamus or prelimbic cortex to locally activate systemically injected JF-NP-26. Light delivery in the thalamus caused rapid and substantial analgesia, and this effect was specific because light delivery in the prelimbic cortex did not relieve BTcP. This finding lays the groundwork for the use of optopharmacology in the treatment of BTcP.

Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain / Notartomaso, Serena; Antenucci, Nico; Liberatore, Francesca; Mascio, Giada; Boccadamo Pompili, Stefano Vito; Font, Joan; Scioli, Mariarosaria; Luongo, Livio; Arcella, Antonietta; Gradini, Roberto; Llebaria, Amadeu; Nicoletti, Ferdinando. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:14(2022), p. 8018. [10.3390/ijms23148018]

Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain

Notartomaso, Serena
Primo
;
Antenucci, Nico
Secondo
;
Liberatore, Francesca;Mascio, Giada;Boccadamo Pompili, Stefano Vito;Arcella, Antonietta;Gradini, Roberto;Nicoletti, Ferdinando
Ultimo
2022

Abstract

Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent analgesic activity, and light-induced activation of one of these compounds (JF-NP-26) in the thalamus was found to induce analgesia in models of inflammatory and neuropathic pain. We used an established mouse model of BTcP based on the injection of cancer cells into the femur, followed, 16 days later, by systemic administration of morphine. BTcP was induced by injection of endothelin-1 (ET-1) into the tumor, 20 min after morphine administration. Mice were implanted with optic fibers delivering light in the visible spectrum (405 nm) in the thalamus or prelimbic cortex to locally activate systemically injected JF-NP-26. Light delivery in the thalamus caused rapid and substantial analgesia, and this effect was specific because light delivery in the prelimbic cortex did not relieve BTcP. This finding lays the groundwork for the use of optopharmacology in the treatment of BTcP.
2022
analgesia; breakthrough cancer pain (BTcP); metabotropic glutamate receptor 5; optopharmacology; thalamus; Analgesics; Analgesics, Opioid; Animals; Disease Models, Animal; Mice; Morphine; Pain Measurement; Thalamus; Analgesia; Breakthrough Pain; Cancer Pain; Neoplasms; Receptors, Metabotropic Glutamate
01 Pubblicazione su rivista::01a Articolo in rivista
Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain / Notartomaso, Serena; Antenucci, Nico; Liberatore, Francesca; Mascio, Giada; Boccadamo Pompili, Stefano Vito; Font, Joan; Scioli, Mariarosaria; Luongo, Livio; Arcella, Antonietta; Gradini, Roberto; Llebaria, Amadeu; Nicoletti, Ferdinando. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:14(2022), p. 8018. [10.3390/ijms23148018]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1657665
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