机构:
Sci Foundry LLC, Dept Biochem & Mol Biol, Orange, CT 06477 USAMonmouth Med Ctr, Dept Pathol, Long Branch, NJ 07740 USA
Cortright, Daniel N.
[2
]
Szallasi, Arpad
论文数: 0引用数: 0
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机构:
Monmouth Med Ctr, Dept Pathol, Long Branch, NJ 07740 USA
Drexel Univ, Coll Med, Philadelphia, PA 19104 USAMonmouth Med Ctr, Dept Pathol, Long Branch, NJ 07740 USA
Szallasi, Arpad
[1
,3
]
机构:
[1] Monmouth Med Ctr, Dept Pathol, Long Branch, NJ 07740 USA
Preclinical research has identified an array of ion channels in sensory neurons involved in the generation and transduction of pain as potential targets for pharmacological intervention. Paramount among these new targets is the family of thermosensitive transient receptor potential channels, referred to as "thermoTRPs". We detect a wide range of noxious stimuli via a limited number (as of today, six) of thermoTRP channels, four of which (TRPV1-TRPV4) respond to heat and two (TRPA1 and TRPM8) are sensitive to cold. Targeting these thermoTRP channels represents a new and logical strategy in pain relief. Unlike traditional analgesic drugs that either suppress inflammation (e. g. NSAIDs and COX-2 inhibitors) or block pain transmission (e. g. opiates), TRP channel inhibitors aim to prevent pain by blocking a receptor where pain is generated. The archetypal thermoTRP is the vanilloid (capsaicin) receptor TRPV1. TRPV1 has a dynamic threshold of activation. Agents in inflammatory soup, including endogenous TRPV1 agonists (so-called "endovanilloids"), act in concert to reduce the heat activation threshold of TRPV1. In patients, the expression of TRPV1 is up-regulated in a number of painful inflammatory disorders. TRPV1 as a pain target has been validated by genetic deletion and pharmacological inhibition experiments. This area of drug development has been moving rapidly. It took less than a decade from the cloning of TRPV1 to clinical trials with potent small molecule TRPV1 antagonists. This review evaluates current evidence that supports particular TRP channels as targets for novel analgesic drugs, along with potential adverse effects that may limit drug development.
机构:
Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
Alessandri-Haber, Nicole
;
Dina, Olayinka A.
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机构:Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
Dina, Olayinka A.
;
Joseph, Elizabeth K.
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机构:Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
Joseph, Elizabeth K.
;
Reichling, David B.
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h-index: 0
机构:Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
Reichling, David B.
;
Levine, Jon D.
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机构:Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
机构:
Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
Alessandri-Haber, Nicole
;
Dina, Olayinka A.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
Dina, Olayinka A.
;
Joseph, Elizabeth K.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
Joseph, Elizabeth K.
;
Reichling, David B.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA
Reichling, David B.
;
Levine, Jon D.
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Oral & Maxillofacial Surg & Med, San Francisco, CA 94143 USA