RT Journal Article
T1 IQM-PC332, a Novel DREAM Ligand with Antinociceptive Effect on Peripheral Nerve Injury-Induced Pain
A1 Socuéllamos, Paula G.
A1 Olivos Ore, Luis Alcides
A1 Barahona Gomáriz, María Victoria
A1 Cercós, Pilar
A1 Pérez Pascual, Marta
A1 Arribas Blázquez, Marina
A1 Naranjo, José Ramón
A1 Valenzuela, Carmen
A1 Gutiérrez Rodríguez, Marta
A1 Rodríguez Artalejo, Antonio
AB 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.
PB MPDI
SN 1422-0067
YR 2022
FD 2022-02-12
LK https://hdl.handle.net/20.500.14352/71744
UL https://hdl.handle.net/20.500.14352/71744
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)/FEDER
NO Instituto de Salud Carlos III (ISCIII)
NO Universidad Complutense
NO Consejo Superior de Investigaciones Científicas (CSIC)
DS Docta Complutense
RD 6 jul 2025