Special Issue "Animal Toxins Targeting Ion Channels Involved in Pain"

Guest Editor
Prof. Dr. Glenn F. King
Division of Chemistry & Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
Website: http://imb.uq.edu.au
E-Mail: glenn.king@imb.uq.edu.au
Phone: +61 7 3346-2025
Fax: +61 7 3346-2101

Guest Editor
Dr. Lachlan Rash
Division of Chemistry & Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
Website: http://imb.uq.edu.au
E-Mail: l.rash@imb.uq.edu.au
Phone: +61 7 3346-2985

Dear Colleagues,

Normal pain is a key adaptive response that serves to limit our exposure to potentially damaging or life-threatening events. In contrast, aberrant long-lasting pain transforms this adaptive response into a debilitating and often poorly managed disease. In 2007, global sales of pain medications totalled $34 billion, highlighting the pervasive nature of this medical condition. Unfortunately, very few drugs are available for the treatment of chronic pain, and most of these have limited efficacy and undesirable side-effects.

A variety of ion channels and receptors are involved sensing pain, including voltage-gated sodium (Na_V) channels, voltage-gated calcium (Ca_V) channels, transient receptor potential (TRP) channels, acid-sensing ion channels (ASICs), and GABA_B, P2X, and nicotinic acetylcholine (nAChR) receptors. In many cases, peptides derived from animal venoms are the most potent and selective modulators of these channels and receptors. As a result, venom peptides have been used extensively for characterizing these channels and receptors, and for their validation as analgesic targets. Moreover, some of these venom peptides are being developed as therapeutics. One venom peptide (Prialt®) has been approved by the FDA for the treatment of chronic pain, while several others are undergoing clinical trials (Xen2174 and CBSB004) or are in various stages of preclinical development. The aim of this special edition of Toxins is to review the potential of venom-derived peptides as leads for the development of novel analgesics.

Articles for this special edition are by invitation only. Authors wishing to submit an article to the special edition should submit a synopsis of no more than 250 words to either of the guest editors for consideration. The article must be aligned with the topic and preference will be given to toxins with potential as therapeutics or as leads for therapeutic development, or toxins that have facilitated the validation of novel analgesic targets.

Prof. Glenn King
Dr. Lachlan Rash
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. 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. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). 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.

• chronic pain
• cone snail
• drug
• inflammatory pain
• neuropathic pain
• nociception
• pain
• peptide
• protein
• scorpion
• snake
• spider
• therapeutic
• venom

Type of Paper: Review
Title: Venom Toxins as a Rich Source of Ca_v2.2 Inhibitors
Authors: Silmara R. de Sousa, Irina Vetter and Richard Lewis
Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia; E-Mails: s.desousa@imb.uq.edu.au (SRS); i.vetter@imb.uq.edu.au (IV); r.lewis@imb.uq.edu.au (RL)
Abstract: Ca_v2.2 is a calcium channel subtype localized at the terminal of nociceptive fibers, where it initiates neurotransmitter release. Hence, Ca_v2.2 participates in the ascending pain pathways, and it is upregulated in the spinal cord in chronic pain states along with the auxiliary α2δ1subunit. It is therefore not surprising that toxins that inhibit Ca_v2.2 are analgesics. A diversity of venomous animals, such as cone snails and spiders, are rich sources of remarkably potent Ca_v2.2 inhibitor toxins. Despite this diversity, Ca_v2.2 blockers still remain unexploited. Recent technological advances, including the establishment of new high throughput assays, may support new discoveries. Here we review the potential of venom toxins as drug leads, as well as some of the current efforts in the discovery of novel Ca_v2.2 inhibitors from nature, and future prospects.

Type of Paper: Review
Title: Analgesic Potential of Venom Peptides that Target Acid Sensing Ion Channels
Authors: Lachlan D. Rash, Natalie Saez, Jonas Jensen and Glenn F. King
Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia; E-Mails: l.rash@imb.uq.edu.au (L.D.R.); n.saez@imb.uq.edu.au (N.S.), j.jensen@imb.uq.edu.au (J.J.); glenn.king@imb.uq.edu.au (G.F.K.)
Abstract: A marked decrease in pH, or acidosis, is often associated with painful pathological conditions such as inflammation, ischemia, trauma, infection, and malignant tumours. Acid sensing ion channels (ASICs) are activated by the drops in pH reached during acidosis (~pH 6-6.5) and they are the primary neuronal proton sensors in mammals. ASICs are highly expressed in small sensory neurons and they play a central role in pain perception. Activation of either ASIC1a or ASIC3 induces pain-related behavior and inhibition of these channels provides analgesia in several animal models of pain. Moreover, ASIC1a inhibition has been shown to be analgesic in humans. The two most potent and selective ASIC inhibitors currently known are venom peptides. Here we review the evidence for the role of ASICs in pain detection and transmission and the therapeutic potential of venom peptides that target ASICs.