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

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 cli...

Full description

Saved in:

Bibliographic Details
Published in:	International journal of molecular sciences Vol. 23; no. 4; p. 2142
Main Authors:	Socuéllamos, Paula G, Olivos-Oré, Luis A, Barahona, María Victoria, Cercós, Pilar, Pérez Pascual, Marta, Arribas-Blázquez, Marina, Naranjo, José Ramón, Valenzuela, Carmen, Gutiérrez-Rodríguez, Marta, Artalejo, Antonio R
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 15-02-2022 MDPI
Subjects:	Analgesics Analgesics - pharmacology Animals Calcium channels Calcium channels (T-type) Calcium channels (voltage-gated) Calcium ions Capsaicin receptors chronic constriction nerve-injury Chronic pain Dorsal root ganglia dorsal root ganglion neuron DREAM ligands DREAM/KChIP3/calsenilin Drug development Drug dosages Ganglia, Spinal - drug effects Ganglia, Spinal - metabolism Hyperalgesia - drug therapy Hyperalgesia - metabolism Information processing Ion channels Kv Channel-Interacting Proteins - metabolism Lead compounds Ligands Male Membrane Potentials - drug effects Neuralgia - drug therapy Neuralgia - etiology Neuralgia - metabolism Neurons neuropathic pain nociception Pain Pain perception Peripheral Nerve Injuries - complications Peripheral Nerve Injuries - metabolism Peripheral nerves Potassium Potassium channels (voltage-gated) Potassium currents Proteins Rats Rats, Sprague-Dawley Sciatic nerve Sciatic Nerve - drug effects Sciatic Nerve - metabolism Sensory neurons Sensory Receptor Cells - drug effects Sensory Receptor Cells - metabolism Surgery Thermal resistance Transient receptor potential proteins DREAM ligands nociception neuropathic pain chronic constriction nerve-injury dorsal root ganglion neuron DREAM/KChIP3/calsenilin
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 ED 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 Ca 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms23042142