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Text
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URL Address
<a href="http://doi.org/10.1124/pr.55.1.1" target="_blank" rel="noreferrer">http://doi.org/10.1124/pr.55.1.1</a>
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Title
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Topical and peripherally acting analgesics
Publisher
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Pharmacological Reviews
Date
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2003
Subject
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Humans; Animals; Non-U.S. Gov't; Research Support; Administration; Neurons; Peripheral Nervous System/drug effects; Topical; Afferent/drug effects/metabolism/physiology; Analgesics/administration & dosage/pharmacology/therapeutic use; Nociceptors/metabolism/physiology; Pain/drug therapy/metabolism/physiopathology; Signal Transduction/drug effects/physiology
Creator
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Sawynok J
Description
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Acute nociceptive, inflammatory, and neuropathic pain all depend to some degree on the peripheral activation of primary sensory afferent neurons. The localized peripheral administration of drugs, such as by topical application, can potentially optimize drug concentrations at the site of origin of the pain, while leading to lower systemic levels and fewer adverse systemic effects, fewer drug interactions, and no need to titrate doses into a therapeutic range compared with systemic administration. Primary sensory afferent neurons can be activated by a range of inflammatory mediators such as prostanoids, bradykinin, ATP, histamine, and serotonin, and inhibiting their actions represents a strategy for the development of analgesics. Peripheral nerve endings also express a variety of inhibitory neuroreceptors such as opioid, alpha-adrenergic, cholinergic, adenosine and cannabinoid receptors, and agonists for these receptors also represent viable targets for drug development. At present, topical and other forms of peripheral administration of nonsteroidal anti-inflammatory drugs, opioids, capsaicin, local anesthetics, and alpha-adrenoceptor agonists are being used in a variety of clinical states. There also are some clinical data on the use of topical antidepressants and glutamate receptor antagonists. There are preclinical data supporting the potential for development of local formulations of adenosine agonists, cannabinoid agonists, cholinergic ligands, cytokine antagonists, bradykinin antagonists, ATP antagonists, biogenic amine antagonists, neuropeptide antagonists, and agents that alter the availability of nerve growth factor. Given that activation of sensory neurons involves multiple mediators, combinations of agents targeting different mechanisms may be particularly useful. Topical analgesics represent a promising area for future drug development.
2003
Identifier
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<a href="http://doi.org/10.1124/pr.55.1.1" target="_blank" rel="noreferrer">10.1124/pr.55.1.1</a>
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Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Type
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Journal Article
2003
Administration
Afferent/drug effects/metabolism/physiology
Analgesics/administration & dosage/pharmacology/therapeutic use
Animals
Backlog
Humans
Journal Article
Neurons
Nociceptors/metabolism/physiology
Non-U.S. Gov't
Pain/drug therapy/metabolism/physiopathology
Peripheral Nervous System/drug effects
Pharmacological Reviews
Research Support
Sawynok J
Signal Transduction/drug effects/physiology
Topical