TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor.
Abstract
Detection of external irritants by head nociceptor neurons has deep evolutionary roots.
Irritant-induced aversive behavior is a popular pain model in laboratory animals.
It is used widely in the formalin model, where formaldehyde is injected into the rodent
paw, eliciting quantifiable nocifensive behavior that has a direct, tissue-injury-evoked
phase, and a subsequent tonic phase caused by neural maladaptation. The formalin model
has elucidated many antipain compounds and pain-modulating signaling pathways. We
have adopted this model to trigeminally innervated territories in mice. In addition,
we examined the involvement of TRPV4 channels in formalin-evoked trigeminal pain behavior
because TRPV4 is abundantly expressed in trigeminal ganglion (TG) sensory neurons,
and because we have recently defined TRPV4's role in response to airborne irritants
and in a model for temporomandibular joint pain. We found TRPV4 to be important for
trigeminal nocifensive behavior evoked by formalin whisker pad injections. This conclusion
is supported by studies with Trpv4(-/-) mice and TRPV4-specific antagonists. Our results
imply TRPV4 in MEK-ERK activation in TG sensory neurons. Furthermore, cellular studies
in primary TG neurons and in heterologous TRPV4-expressing cells suggest that TRPV4
can be activated directly by formalin to gate Ca(2+). Using TRPA1-blocker and Trpa1(-/-)
mice, we found that both TRP channels co-contribute to the formalin trigeminal pain
response. These results imply TRPV4 as an important signaling molecule in irritation-evoked
trigeminal pain. TRPV4-antagonistic therapies can therefore be envisioned as novel
analgesics, possibly for specific targeting of trigeminal pain disorders, such as
migraine, headaches, temporomandibular joint, facial, and dental pain, and irritation
of trigeminally innervated surface epithelia.
Type
Journal articleSubject
ERKFormalin model
Formalin receptor
Irritant
MEK
TRPV4
Trigeminal ganglion
Trigeminal pain
Whisker pad
Animals
Butadienes
Cells, Cultured
Disease Models, Animal
Enzyme Inhibitors
Extracellular Signal-Regulated MAP Kinases
Fixatives
Formaldehyde
Keratinocytes
Membrane Potentials
Mice
Mice, Inbred C57BL
Mice, Transgenic
Morpholines
Neurons
Nitriles
Pain
Pyrroles
TRPV Cation Channels
Trigeminal Ganglion
Ubiquitin Thiolesterase
Vibrissae
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https://hdl.handle.net/10161/12970Published Version (Please cite this version)
10.1016/j.pain.2014.09.033Publication Info
Chen, Yong; Kanju, Patrick; Fang, Quan; Lee, Suk Hee; Parekh, Puja K; Lee, Whasil;
... Liedtke, Wolfgang (2014). TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin
receptor. Pain, 155(12). pp. 2662-2672. 10.1016/j.pain.2014.09.033. Retrieved from https://hdl.handle.net/10161/12970.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Yong Chen
Associate Professor in Neurology
Wolfgang Bernhard Liedtke
Adjunct Professor in the Department of Neurology
Research Interests in the Liedtke-Lab:
Pain/ nociception
Sensory transduction and -transmission
TRP ion channels
Water and salt equilibrium regulated by the central nervous system
Visit the lab's website, download papers and read Dr. Liedtke's CV here.
Carlene D Moore
Assistant Professor in Neurology
Fan Wang
Adjunct Professor in the Department of Neurobiology
My lab studies neural circuit basis of sensory perception. Specifically we are interested
in determining neural circuits underlying (1) active touch sensation including tactile
processing stream and motor control of touch sensors on the face; (2) pain sensation
including both sensory-discriminative and affective aspects of pain; and (3) general
anesthesia including the active pain-suppression process. We use a combination of
genetic, viral, electrophysiology, and in vivo imaging (in f
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