IQM-PC332, a Novel DREAM Ligand with Antinociceptive Effect on Peripheral Nerve Injury-Induced Pain



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Socuéllamos, Paula G. and Olivos Oré, Luis Alices and Barahona Gomariz, María Victoria and Cercós, Pilar and Pérez Pascual, Marta and Arribas Blázquez, Marina and Naranjo, José Ramón and Valenzuela, Carmen and Gutiérrez Rodríguez, Marta and Rodríguez Artalejo, Antonio (2022) IQM-PC332, a Novel DREAM Ligand with Antinociceptive Effect on Peripheral Nerve Injury-Induced Pain. International Journal of Molecular Sciences, 23 (4). p. 2142. ISSN 1422-0067

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Neuropathic pain is a form of chronic pain arising from damage of the neural cells that sense, transmit or process sensory information. Given its growing prevalence and common refractoriness to conventional analgesics, the development of new drugs with pain relief effects constitutes a prominent clinical need. In this respect, drugs that reduce activity of sensory neurons by modulating ion channels hold the promise to become effective analgesics. Here, we evaluated the mechanical antinociceptive effect of IQM-PC332, a novel ligand of the multifunctional protein downstream regulatory element antagonist modulator (DREAM) in rats subjected to chronic constriction injury of the sciatic nerve as a model of neuropathic pain. IQM-PC332 administered by intraplantar (0.01–10 µg) or intraperitoneal (0.02–1 µg/kg) injection reduced mechanical sensitivity by ≈100% of the maximum possible effect, with ED50 of 0.27 ± 0.05 µg and 0.09 ± 0.01 µg/kg, respectively. Perforated-patch whole-cell recordings in isolated dorsal root ganglion (DRG) neurons showed that IQM-PC332 (1 and 10 µM) reduced ionic currents through voltage-gated K+ channels responsible for A-type potassium currents, low, T-type, and high voltage-activated Ca2+ channels, and transient receptor potential vanilloid-1 (TRPV1) channels. Furthermore, IQM-PC332 (1 µM) reduced electrically evoked action potentials in DRG neurons from neuropathic animals. It is suggested that by modulating multiple DREAM–ion channel signaling complexes, IQM-PC332 may serve a lead compound of novel multimodal analgesics.

Item Type:Article
Uncontrolled Keywords:DREAM/KChIP3/calsenilin; DREAM ligands; neuropathic pain; nociception; chronic constriction nerve-injury; dorsal root ganglion neuron
Subjects:Medical sciences > Medicine > Gynecology and Obstetrics
Medical sciences > Medicine > Neurosciences
ID Code:73372
Deposited On:05 Jul 2022 13:54
Last Modified:06 Jul 2022 07:29

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