Pain, one of the oldest medical problems still remains an immense clinical challenge. Our ability to effectively treat acute and especially chronic painful conditions often causes other unwanted side-effects that degrade the quality of life. TRPV1, also known as the capsaicin receptor, has been at the forefront of research focused on the development of new strategies to treat chronic painful conditions that arise from inflammation. TRPV1 is expressed in primary afferent nociceptors (specialized sensory neurons) that detect painful stimuli and its expression is increased in these nerve cells under conditions of inflammation. Increased levels of TRPV1 appear to drive the development of persistent pain and hyperalgesia. Surprisingly, little is known about what controls the production of TRPV1 in the nervous system under normal or inflammatory conditions. The current project is focused on: 1) Understanding how inflammatory mediators released at the site of injury, such as Nerve Growth Factor (NGF), increase TRPV1 production under conditions of inflammation. We have recently demonstrated that NGF positively regulates the transcriptional control regions in the rat TRPV1 gene. Based on additional data, we now propose to study a link between the Sp1- like family of transcription factors and NGF / inflammation mediated increases in TRPV1 dependent pain. 2) Another area of study is the regulation of TRPV1 expressed activity through its co-expression with other TRPV1 splice variants. Previously, we identified a TRPV1 splice variant (VR.5'sv) that when co-expressed, blocks TRPV1 activation to noxious stimuli in vitro. We now propose to study the physiologic consequence of VR.5'sv and other TRPV1 splice variants in individual sensory neurons. By studying the individual response properties of nociceptive neurons and matching these responses to a molecular signature of splice variant expression, we will determine the role of TRPV1 splice variants in the control of nociceptor activation and pain transduction.

Public Health Relevance

The basis for chronic pain arising from inflammatory conditions is poorly understood. The receptor that detects the burning sensation to pungent hot chili peppers is important for maintaining inflammatory pain in sensory nerves. We are studying a way to reduce or turn off the production of this receptor in sensory nerves as a way to control the pain from chronic peripheral inflammation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Chen, Daofen
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Zavala, K; Lee, J; Chong, J et al. (2014) The anticancer antibiotic mithramycin-A inhibits TRPV1 expression in dorsal root ganglion neurons. Neurosci Lett 578:211-6
Chu, Catherine; Zavala, Kathryn; Fahimi, Atefeh et al. (2011) Transcription factors Sp1 and Sp4 regulate TRPV1 gene expression in rat sensory neurons. Mol Pain 7:44
Schumacher, Mark A; Eilers, Helge (2010) TRPV1 splice variants: structure and function. Front Biosci (Landmark Ed) 15:872-82
Schumacher, Mark A (2010) Transient receptor potential channels in pain and inflammation: therapeutic opportunities. Pain Pract 10:185-200
Eilers, Helge; Lee, Sook-Young; Hau, Cathy W et al. (2007) The rat vanilloid receptor splice variant VR.5'sv blocks TRPV1 activation. Neuroreport 18:969-73
Xue, Qing; Jong, Beverly; Chen, Tom et al. (2007) Transcription of rat TRPV1 utilizes a dual promoter system that is positively regulated by nerve growth factor. J Neurochem 101:212-22
Xue, Q; Yu, Y; Trilk, S L et al. (2001) The genomic organization of the gene encoding the vanilloid receptor: evidence for multiple splice variants. Genomics 76:14-20
Schumacher, M A; Moff, I; Sudanagunta, S P et al. (2000) Molecular cloning of an N-terminal splice variant of the capsaicin receptor. Loss of N-terminal domain suggests functional divergence among capsaicin receptor subtypes. J Biol Chem 275:2756-62
Schumacher, M A; Jong, B E; Frey, S L et al. (2000) The stretch-inactivated channel, a vanilloid receptor variant, is expressed in small-diameter sensory neurons in the rat. Neurosci Lett 287:215-8