Journal ArticleDOI
Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor
Michael J. Caterina,A. Leffler,Annika B. Malmberg,William J. Martin,Jodie A. Trafton,K. R. Petersen-Zeitz,Martin Koltzenburg,Allan I. Basbaum,David Julius +8 more
TLDR
Sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli and are impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation.Abstract:
The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (>43 degrees C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.read more
Citations
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Journal ArticleDOI
Hot flash: TRPV channels in the brain.
Julie A. Kauer,Helen E. Gibson +1 more
TL;DR: Evidence that TRPV channels in the central nervous system might contribute to many basic neuronal functions including resting membrane potential, neurotransmitter release and synaptic plasticity is reviewed.
Journal ArticleDOI
Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators.
Nobuaki Takahashi,Yusuke Mizuno,Daisuke Kozai,Shinichiro Yamamoto,Shigeki Kiyonaka,Takahiro Shibata,Koji Uchida,Yasuo Mori +7 more
TL;DR: It is shown that a variety of inflammatory mediators (15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), nitric oxide (NO), hydrogen peroxide (H2O2), and proton (H+) activate human TRPA1 heterologously expressed in HEK cells.
Journal ArticleDOI
Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents
Amol M. Patwardhan,Armen N. Akopian,Nikita B. Ruparel,Anibal R. Diogenes,Susan E Weintraub,Charis L. Uhlson,Robert C. Murphy,Kenneth M. Hargreaves +7 more
TL;DR: These findings suggest a mechanism for integrating the hyperalgesic and proinflammatory roles of TRPV1 and linoleic acid metabolites and may provide the foundation for investigating new classes of analgesic drugs.
Journal ArticleDOI
Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel
Fan Yang,Xian Xiao,Wei Cheng,Wei Yang,Peilin Yu,Song Zhenzhen,Vladimir Yarov-Yarovoy,Jie Zheng +7 more
TL;DR: This study provided a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrated an effective approach to obtain atomic level information from cryo-EM structures.
Journal ArticleDOI
The Transient Receptor Potential Vanilloid-1 Channel in Thermoregulation: A Thermosensor It Is Not
Andrej A. Romanovsky,Maria Camila Almeida,András Garami,Alexandre A. Steiner,Alexandre A. Steiner,Mark H. Norman,Shaun F. Morrison,Kazuhiro Nakamura,Kazuhiro Nakamura,Jeffrey J. Burmeister,Tatiane B. Nucci +10 more
TL;DR: It is concluded that this channel does not serve as a thermosensor, at least not under physiological conditions, and all thermoregulatory responses to TRPV1 agonists and antagonists stem from primary actions on these two neuronal populations.
References
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Journal ArticleDOI
The capsaicin receptor: a heat-activated ion channel in the pain pathway
Michael J. Caterina,Mark Schumacher,Makoto Tominaga,Tobias A. Rosen,Jon D. Levine,David Julius +5 more
TL;DR: The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo.
Journal ArticleDOI
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.
TL;DR: Both the thermal method and the Randall‐Selitto mechanical method detected dose‐related hyperalgesia and its blockade by either morphine or indomethacin, but the Thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.
Journal ArticleDOI
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
Peter M. Zygmunt,Jesper Petersson,David Andersson,Huai-hu Chuang,Morten Sørgård,Vincenzo Di Marzo,David Julius,Edward D. Högestätt +7 more
TL;DR: It is shown that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin-gene-related peptide (CGRP), which indicates that the vanilloid receptor may be another molecular target for endogenousAnandamide, besides cannabinoid receptors, in the nervous and cardiovascular systems.
Journal Article
Vanilloid (Capsaicin) Receptors and Mechanisms
Arpad Szallasi,Peter M. Blumberg +1 more
TL;DR: This paper focuses on hot pepper, which is eaten on a daily basis by an estimated one-quarter of the world’s population and has potential to be a biological target for regenerative medicine.