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
Mechanisms of sensitization of the response of single dorsal root ganglion cells from adult rat to noxious heat
TL;DR: It is concluded that the response of dorsal root ganglion neurons to noxious heat is conditioned by nerve growth factor in the same way as their response to capsaicin and that these responses require the presence of trkA and TRPV1.
Journal ArticleDOI
Development, plasticity and modulation of visceral afferents
Julie A. Christianson,Klaus Bielefeldt,Christophe Altier,Nicolas Cenac,Brian M. Davis,Gerald F. Gebhart,Karin W. High,Marian Kollarik,Alan Randich,Brad Undem,Nathalie Vergnolle +10 more
TL;DR: A review examines recent insights into visceral afferent anatomy and neurochemistry and how neonatal insults can affect the function of these neurons in the adult and new approaches to the treatment of visceral pain.
Journal ArticleDOI
Swelling-activated calcium signalling in cultured mouse primary sensory neurons.
TL;DR: It is suggested that hypo‐osmotic stimulation activates several Ca2+‐influx pathways, including Gd3+‐sensitive stretch‐activated ion channels, in a large fraction of trigeminal ganglion neurons.
Journal ArticleDOI
Somatostatin modulates the transient receptor potential vanilloid 1 (TRPV1) ion channel
Susan M. Carlton,Shengtai Zhou,Junhui Du,Gregory L. Hargett,Guangchen Ji,Richard E. Coggeshall +5 more
TL;DR: The present study provides several lines of evidence that an important mechanism underlying SSTR modulation of nociceptors is regulation of the transient receptor potential vanilloid 1 ion channel (TRPV1, formerly the VR1 receptor).
Journal ArticleDOI
Pharmacology of Modality-Specific Transient Receptor Potential Vanilloid-1 Antagonists That Do Not Alter Body Temperature
Regina M. Reilly,Heath A. McDonald,Pamela S. Puttfarcken,Shailen K. Joshi,La Geisha Lewis,Madhavi Pai,Pamela H. Franklin,Jason A. Segreti,Torben R. Neelands,Ping Han,Jun Chen,Patrick W. Mantyh,Joseph R. Ghilardi,Teresa M. Turner,Voight Eric,Jerome F. Daanen,Robert G. Schmidt,Arthur Gomtsyan,Michael E. Kort,Connie R. Faltynek,Philip R. Kym +20 more
TL;DR: Comparison of the in vitro pharmacological properties of these TRPV1 antagonists with their in vivo effects on core body temperature confirms and expands earlier observations that acid-sparing TRPv1 antagonists do not significantly increase coreBody temperature.
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.