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
Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans.
TL;DR: Exposure to mammalian TRPV4 in ASH neurons of osm-9 worms restored avoidance responses to hypertonicity and nose touch, but not the response to odorant repellents, providing evidence that TRpV4 can function as a component of an osmotic/mechanical sensor in vivo.
Journal ArticleDOI
TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
Víctor M. Meseguer,Yeranddy A. Alpizar,Enoch Luis,Sendoa Tajada,Bristol Denlinger,Otto Fajardo,Jan-Albert Manenschijn,Carlos Fernández-Peña,Arturo Talavera,Tatiana Kichko,Belén Navia,Alicia Sanchez,Rosa Señarís,Peter W. Reeh,M. T. Pérez-García,José R. López-López,Thomas Voets,Carlos Belmonte,Karel Talavera,Félix Viana +19 more
TL;DR: This work shows that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity, and finds that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent onTRPA1 channel activation in nocICEptive sensory neurons, and develop independently of TLR4 activation.
Journal ArticleDOI
Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia
Ji-eun Shin,Hawon Cho,Sun Wook Hwang,Jooyoung Jung,Chan Young Shin,Soon Youl Lee,So Hee Kim,Myung Gull Lee,Young Hae Choi,Jinwoong Kim,Nicole Alessandri Haber,David B. Reichling,Sachia G. Khasar,Jon D. Levine,Uhtaek Oh +14 more
TL;DR: Bristolkinin, acting at B2 bradykinin receptors, excites sensory nerve endings by activating capsaicin receptors via production of 12-lipoxygenase metabolites of arachidonic acid, identifying a mechanism that might be targeted in the development of new therapeutic strategies for the treatment of inflammatory pain.
Journal ArticleDOI
TRP channels: targets for the relief of pain.
TL;DR: Transient Receptor Potential channels have emerged as a family of evolutionarily conserved ligand-gated ion channels that contribute to the detection of physical stimuli and contribute to pain hypersensitivity associated with peripheral inflammatory and neuropathic pain states.
Journal ArticleDOI
Two Interdependent TRPV Channel Subunits, Inactive and Nanchung, Mediate Hearing in Drosophila
Zhefeng Gong,Wonseok Son,Yun Doo Chung,Janghwan Kim,Dong Wook Shin,Colleen A. McClung,Yong Lee,Hye Won Lee,Deok-Jin Chang,Bong-Kiun Kaang,Hawon Cho,Uhtaek Oh,Jay Hirsh,Maurice J. Kernan,Changsoo Kim +14 more
TL;DR: The IAV protein forms a hypotonically activated channel when expressed in cultured cells; in flies, it is specifically expressed in the chordotonal neurons, localized to their cilia and required for hearing.
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.