http://www.mdpi.com/journal/pharmaceuticals/special_issues/ion-channels/ Dear Colleagues, Pain still remains an immense clinical challenge. Our ability to effectively treat acute and especially chronic painful conditions often causes unwanted side-effects that degrade the quality of life. The last decade has seen an explosive growth in our understanding of how the sensation of pain is initiated at the peripheral terminals of primary afferent neurons – nociceptors. These specialized nerve terminals express a diverse array of ion channel - receptors that transduce noxious chemical, thermal and mechanical stimuli. Together, these ion channels serve to detect impending and ongoing tissue damage arising from pathophysiologic states such as inflammation and nerve injury. This section will focus on the therapeutic potential of targeting specific ion channels expressed in nociceptors to more effectively treat painful conditions. Prof. Dr. Mark A. Schumacher Guest Editor Submission All manuscripts should be submitted to pharmaceuticals@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website. Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed Open Access monthly journal published by MDPI.   Please visit the Instructions for Authors page before submitting a manuscript. Article Processing Charges (APC) for publication in this Open Access journal will be waived for well-prepared manuscripts submitted before 30 June 2010. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections. http://www.mdpi.com/1424-8247/3/9/2768/ We are normally unaware of the complex signalling events which continuously occur within our internal organs. Most of us only become cognisant when sensations of hunger, fullness, urgency or gas arise. However, for patients with organic and functional bowel disorders pain is an unpleasant and often debilitating reminder. Furthermore, chronic pain still represents a large unmet need for clinical treatment. Consequently, chronic pain has a considerable economic impact on health care systems and the afflicted individuals. In order to address this need we must understand how symptoms are generated within the gut, the molecular pathways responsible for generating these signals and how this process changes in disease states. http://www.mdpi.com/1424-8247/3/9/2768/ Thu, 26 Aug 2010 00:00:00 CEST Pharmaceuticals 2010-08-26 3 9 Review 2768 2798 1424-8247 Identifying the Ion Channels Responsible for Signaling Gastro-Intestinal Based Pain 2010-08-26 doi: 10.3390/ph3092768 Stuart M. Brierley Patrick A. Hughes Andrea M. Harrington Grigori Y. Rychkov L. Ashley Blackshaw http://www.mdpi.com/1424-8247/3/7/2248/ The expression of multiple ion channels and receptors is essential for nociceptors to detect noxious stimuli of a thermal, mechanical or chemical nature. The peripheral sensory transduction systems of the urinary bladder include sensory nerve endings, urothelial cells and others whose location is suitable for transducing mechanical and chemical stimuli. There is an increasing body of evidence implicating the Deg/ENaC and TRP channel families in the control of bladder afferent excitability under physiological and pathological conditions. Pharmacological interventions targeting these ion channels may provide a new strategy for the treatment of pathological bladder sensation and pain. http://www.mdpi.com/1424-8247/3/7/2248/ Mon, 19 Jul 2010 00:00:00 CEST Pharmaceuticals 2010-07-19 3 7 Review 2248 2267 1424-8247 Emerging Families of Ion Channels Involved in Urinary Bladder Nociception 2010-07-19 doi: 10.3390/ph3072248 Isao Araki Mitsuharu Yoshiyama Hideki Kobayashi Tsutomu Mochizuki Shuqi Du Yusaku Okada Masayuki Takeda http://www.mdpi.com/1424-8247/3/7/2178/ For over 160 years, general anesthetics have been given for the relief of pain and suffering. While many theories of anesthetic action have been purported, it has become increasingly apparent that a significant molecular focus of anesthetic action lies within the family of ligand-gated ion channels (LGIC’s). These protein channels have a transmembrane region that is composed of a pentamer of four helix bundles, symmetrically arranged around a central pore for ion passage. While initial and some current models suggest a possible cavity for binding within this four helix bundle, newer calculations postulate that the actual cavity for anesthetic binding may exist between four helix bundles. In either scenario, these cavities have a transmembrane mode of access and may be partially bordered by lipid moieties. Their physicochemical nature is amphiphilic. Anesthetic binding may alter the overall motion of a ligand-gated ion channel by a “foot-in-door” motif, resulting in the higher likelihood of and greater time spent in a specific channel state. The overall gating motion of these channels is consistent with that shown in normal mode analyses carried out both in vacuo as well as in explicitly hydrated lipid bilayer models. Molecular docking and large scale molecular dynamics calculations may now begin to show a more exact mode by which anesthetic molecules actually localize themselves and bind to specific protein sites within LGIC’s, making the design of future improvements to anesthetic ligands a more realizable possibility. http://www.mdpi.com/1424-8247/3/7/2178/ Thu, 08 Jul 2010 00:00:00 CEST Pharmaceuticals 2010-07-08 3 7 Review 2178 2196 1424-8247 The Molecular Mechanisms of Anesthetic Action: Updates and Cutting Edge Developments from the Field of Molecular Modeling 2010-07-08 doi: 10.3390/ph3072178 Bertaccini http://www.mdpi.com/1424-8247/3/5/1411/ Pathophysiological conditions such as inflammation, ischemia, infection and tissue injury can all evoke pain, and each is accompanied by local acidosis. Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. Increasing evidence suggests that ASICs represent essential sensors for tissue acidosis-related pain. This review provides an update on the role of ASICs in pain sensation and discusses their therapeutic potential for pain management. http://www.mdpi.com/1424-8247/3/5/1411/ Tue, 11 May 2010 00:00:00 CEST Pharmaceuticals 2010-05-11 3 5 Review 1411 1425 1424-8247 Acid-Sensing Ion Channels and Pain 2010-05-11 doi: 10.3390/ph3051411 Gu Lee