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Pharmaceuticals
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Ion Channels as Therapeutic Targets for Pain
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Ion Channels as Therapeutic Targets for Pain

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 April 2010) | Viewed by 39498

Special Issue Editor

Prof. Dr. Mark A. Schumacher

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

Special Issue Information

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

Keywords

  • 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

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Published Papers (4 papers)

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Review

563 KiB  
Review
Identifying the Ion Channels Responsible for Signaling Gastro-Intestinal Based Pain
by Stuart M. Brierley, Patrick A. Hughes, Andrea M. Harrington, Grigori Y. Rychkov and L. Ashley Blackshaw
Pharmaceuticals 2010, 3(9), 2768-2798; https://doi.org/10.3390/ph3092768 - 26 Aug 2010
Cited by 14 | Viewed by 8934
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Ion Channels as Therapeutic Targets for Pain)
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203 KiB  
Review
Emerging Families of Ion Channels Involved in Urinary Bladder Nociception
by Isao Araki, Mitsuharu Yoshiyama, Hideki Kobayashi, Tsutomu Mochizuki, Shuqi Du, Yusaku Okada and Masayuki Takeda
Pharmaceuticals 2010, 3(7), 2248-2267; https://doi.org/10.3390/ph3072248 - 19 Jul 2010
Cited by 7 | Viewed by 10333
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Ion Channels as Therapeutic Targets for Pain)
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Graphical abstract

516 KiB  
Review
The Molecular Mechanisms of Anesthetic Action: Updates and Cutting Edge Developments from the Field of Molecular Modeling
by Edward J. Bertaccini
Pharmaceuticals 2010, 3(7), 2178-2196; https://doi.org/10.3390/ph3072178 - 8 Jul 2010
Cited by 9 | Viewed by 8583
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Ion Channels as Therapeutic Targets for Pain)
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164 KiB  
Review
Acid-Sensing Ion Channels and Pain
by Qihai Gu and Lu-Yuan Lee
Pharmaceuticals 2010, 3(5), 1411-1425; https://doi.org/10.3390/ph3051411 - 11 May 2010
Cited by 27 | Viewed by 11098
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Ion Channels as Therapeutic Targets for Pain)
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