Mechanisms and Modulation of Pain: From Ion Channels to Translational Therapeutics

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (30 June 2026) | Viewed by 474

Editor


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Guest Editor
Human Health Therapeutics, National Research Council of Canada, 1200 Montreal Road, Ottawa, ON K1A0R6, Canada
Interests: pain; analgesia; biologics; central nervous system; sodium channels; in vivo models

Special Issue Information

Dear Colleagues,

Pain is currently defined as an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage. Nociceptive pain is initiated by activation of specialized nerve receptors located in peripheral tissues that detect harmful stimuli; these then generate electrical signals that are transmitted through the nervous system. Pain is a complex condition resulting from the dynamic interplay between the neuronal, immune, and vascular systems. Neuronal plasticity refers to the adaptive changes that occur in the nociceptive pathways, leading to peripheral and central sensitization. This sensitization can result in amplification of pain signals, lowered pain thresholds, and exaggerated perception of normally non-painful stimuli. Numerous cytokines, chemokines, G-protein-coupled receptors, and ion channels are involved in these processes. Specifically, the activation of ion channels in response to specific environmental stimuli allows for the conversion of variable mechanical, thermal, and chemical stimuli into voltage changes in neurons. The various ion channels present in peripheral nerves and dorsal root ganglia are differentially expressed, distributed, phosphorylated, and activated under states of pain.

Currently, opioids, non-steroidal anti-inflammatory drugs, and antidepressants are the mainstays of pain management strategies; nonetheless, management of pain remains challenging due to its complex pathophysiology. In the case of opioids, the risk of physical dependence and tolerance issues is significant. There is great interest in developing more effective and secure therapies that focus on addressing the fundamental causes of persistent pain; novel analgesics targeting various receptors and ion channels are also being investigated.

This Special Issue aims to collect original research articles, review articles, and clinical studies on topics relevant to the ongoing efforts to develop improved therapeutic approaches for pain applications. We are particularly interested in research focused on novel therapeutic targets, efficacy studies on pre-clinical models, and the challenges in translating pain therapies into clinical applications.

Dr. Álvaro Yogi
Guest Editor

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Keywords

  • pain
  • mechanisms
  • signaling pathways
  • ion channels, therapeutic targets
  • neuropathic pain
  • inflammatory pain
  • pre-clinical models

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Published Papers (1 paper)

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Research

24 pages, 8541 KB  
Article
Computational Insights into the Molecular Synergy of Paracetamol and Codeine
by Manuel-Ovidiu Amzoiu, Georgeta Sofia Popescu, Denisa Constantina Amzoiu, Maria Viorica Ciocîlteu, Gabriela Rau, Costel Valentin Manda, Andrei Gresita and Oana Taisescu
Life 2026, 16(7), 1104; https://doi.org/10.3390/life16071104 - 2 Jul 2026
Viewed by 155
Abstract
Combination analgesic therapy is commonly used to improve pain control, yet conventional molecular docking approaches typically evaluate individual ligands and provide limited insight into potential intermolecular associations between co-administered drugs. In this study, paracetamol, codeine, and their proposed 1:1 and 2:1 non-covalent assemblies [...] Read more.
Combination analgesic therapy is commonly used to improve pain control, yet conventional molecular docking approaches typically evaluate individual ligands and provide limited insight into potential intermolecular associations between co-administered drugs. In this study, paracetamol, codeine, and their proposed 1:1 and 2:1 non-covalent assemblies were investigated using lipophilicity analysis, molecular docking, short molecular dynamics relaxation, electrostatic potential surface mapping, and HOMO–LUMO analysis. Docking simulations were performed against cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and the μ-opioid receptor (MOR). The proposed assemblies produced docking scores that differed from those of the individual compounds, with the most pronounced differences observed for the cyclooxygenase targets. The 2:1 assemblies generally exhibited the most favorable docking scores, whereas the predicted interaction profiles at MOR appeared to be more dependent on molecular orientation. Molecular dynamics relaxation and electronic structure analyses further revealed differences in the energetic and electronic characteristics of the investigated configurations. These findings support the theoretical feasibility of distinct interaction patterns among the proposed paracetamol–codeine assemblies within the applied computational framework. However, the reported docking scores represent relative computational values rather than experimentally validated binding affinities, and the short-timescale molecular dynamics simulations provide only preliminary information regarding conformational stability. Furthermore, the existence and biological relevance of the proposed assemblies under physiological conditions remain to be established. This study provides a computational basis for future investigations of intermolecular associations in multicomponent drug systems. Full article
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