Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 708, Issue 1-3, Pages 105-112Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2013.03.001
Keywords
Nerve regeneration; Neuroma; Node of Ranvier; Internode; Voltage-gated ion channels; Acquired channelopathies; Subtype-selective voltage-gated; ion channel blockers; Rodent pain models; Nerve excitability testing
Categories
Funding
- Lundbeck Foundation
- Novo Nordisk Foundation
- Danish Medical Research Council
- Ludvig and Sara Elsass Foundation
- Foundation for Research in Neurology
- Jytte and Kaj Dahlboms Foundation
Ask authors/readers for more resources
Upon peripheral nerve injury (caused by trauma or disease process) axons of the dorsal root ganglion (DRG) somatosensory neurons have the ability to sprout and regrow/remyelinate to reinnervate distant target tissue or form a tangled scar mass called a neuroma. This regenerative response can become maladaptive leading to a persistent and debilitating pain state referred to as chronic pain corresponding to the clinical description of neuropathic/chronic inflammatory pain. There is little agreement to what causes peripheral chronic pain other than hyperactivity of the nociceptive DRG neurons which ultimately depends on the function of voltage-gated ion channels. This review focuses on the pharmacological modulators of voltage-gated ion channels known to be present on axonal membrane which represents by far the largest surface of DRG neurons. Blockers of voltage-gated Na+ channels, openers of voltage-gated K+ channels and blockers of hyperpolarization-activated cyclic nucleotide-gated channels that were found to reduce neuronal activity were also found to be effective in neuropathic and inflammatory pain states. The isoforms of these channels present on nociceptive axons have limited specificity. The rationale for considering axonal voltage-gated ion channels as targets for pain treatment comes from the accumulating evidence that chronic pain states are associated with a dysregulation of these channels that could alter their specificity and make them more susceptible to pharmacological modulation. This drives the need for further development of subtype-specific voltage-gated ion channels modulators, as well as clinically available neurophysiological techniques for monitoring axonal ion channel function in peripheral nerves. (C) 2013 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available