Special Issue "Ion Channels as Therapeutic Targets for Pain"

Guest Editor
Prof. Dr. Mark A. Schumacher
Department of Anesthesia and Perioperative Care, School of Medicine, University of California, San Francisco, 521 Parnassus Avenue, (0648), San Francisco, CA 94143-0648, USA
E-Mail:
Interests: capsaicin receptor; gene; genomics; Nerve Growth Factor (NGF); nociceptor; pain; promoter; splice variant; transcription factor-Sp1; TRPV1; VR1

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.org 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.

• TRP channels
• capsaicin receptor
• TRPV1
• TRPA1
• TRPV4
• P2X
• purinergic receptor
• calcium channel
• ASIC
• acid sensing channel
• sodium channel
• NaV 1.8
• NaV 1.9
• TTX-R sodium channel
• potassium channel – two pore
• pain
• primary afferent nociceptor
• analgesia
• nociception

Type of Paper: Review
Tentative Title: Why in spite of many progresses we still suffer from pain?
Authors: Dieter D’hoedt and Daniel Bertrand; E-Mail: Dieter.Dhoedt@unige.ch (D.D.)
Abstract: Sensations play a decisive role in our day-to-day life and are, at their extreme, ranging from pleasure to pain. An obvious question is why; in spite of the progresses made in our knowledge of neurophysiology we are still limited in our possibilities to treat pain. The aim of this review is a comprehensive overview of the elements involved in sensory perception with their pathways and regulation. Analysis of the determinants transforming normal sensation to pain and its exacerbation of sensory stimuli is discussed in the light of the latest finding in the field of voltage- and ligand-gated channels.

Type of Paper: Review
Tentative Title: Molecular Mechanisms of Anesthetic Action: Updates and Cutting Edge Findings
Author: Edward J. Bertaccini
Affiliation: Stanford University School of Medicine, Stanford, CA, USA; E-Mail: edwardb@stanford.edu
Abstract: For over 160 years, anesthetics have been given for the relief of pain and suffering. While many theories of action have been purported, it is increasingly apparent that a significant molecular focus of anesthetic action lies within the family of ligand-gated ion channels (LGIC's). These channels have a transmembrane region that is composed of a pentamer of four helix bundles. 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. These cavities have a transmembrane mode of access and are clearly amphipathic in nature. 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.

Type of Paper: Review
Title: Acid-Sensing Ion Channels and Pain
Author: Qihai Gu
Affiliation: University of Kentucky Medical Center, Lexington, KY, USA; E-Mail: qgu2@email.uky.edu
Abstract: Many physiological or pathophysiological states, such as inflammation, ischemia, tissue injury and metabolic stress, evoke pain and are accompanied by local acidosis. Acid sensing ion channels (ASICs) are proton-gated cation channels expressed in both central and peripheral nervous systems. Increasing evidence suggest that ASICs represent essential sensors of acid-induced pain. This review provides an update on the role of ASICs in pain sensation and their potential as a therapeutic target for pain management.