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.
Serena NotartomasoNico AntenucciFrancesca LiberatoreGiada MascioStefano Vito Boccadamo PompiliJoan FontMariarosaria ScioliLivio LuongoAntonietta ArcellaRoberto GradiniAmadeu LlebariaFerdinando NicolettiPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- neuropathic pain
- pain management
- chronic pain
- spinal cord
- mouse model
- spinal cord injury
- postoperative pain
- ultrasound guided
- deep brain stimulation
- chronic obstructive pulmonary disease
- squamous cell
- emergency department
- squamous cell carcinoma
- bone mineral density
- functional connectivity
- anti inflammatory
- optical coherence tomography
- human health
- risk assessment
- body composition
- insulin resistance
- blood brain barrier
- postmenopausal women
- skeletal muscle
- cerebral ischemia
- replacement therapy