Pathological pain arising from visceral sensory neurons is integral to organ dysfunction and can occur in the absence of any obvious structural abnormalities (e.g. irritable bowel syndrome). Visceral pain also contributes significantly to the debilitating nature of many chronic diseases (e.g. pain associated with Crohns's disease). The long-term goal in visceral sensory biology is to identify the causes of these persistent pain states and to develop therapies that specifically target these conditions. Recently, significant advances have been made in understating somatic pain. In large part, this is due to the development of molecular and genetic models that allow a greater level of resolution than has been previously possible. It is well established that visceral afferents are very different from somatic afferents [26]. However, if the techniques used to examine somatic nociception could be adapted for visceral sensory systems, equally significant progress could be made to elucidate basic mechanisms underlying visceral pain. To that end, the present experiments combine behavioral, anatomical, physiological and genetic approaches to study visceral afferents in the mouse. A novel """"""""ex vivo"""""""" physiology paradigm that preserves the entire sensory neuron, including its peripheral connection to the organ (in this case the colon) and its central connection to the spinal cord, will be used. This application has 4 specific aims: The first is to determine the heterogeneity of visceral afferents projecting to different abdominal and pelvic organs. The second goal is to use the ex vivo preparation to determine the comprehensive phenotype (CP) of individual visceral sensory neurons. The CP includes an anatomical description of central and peripheral processes, neurochemical characterization, and analysis of action potential shape, conduction velocity and response properties (e.g. threshold, adequate stimulus typing). This information is crucial for the third goal, which is to determine how different populations of visceral afferents (identified on the basis of the CP) respond to insult. For the fourth aim we will repeat these studies in mice lacking the transient receptor potential vaniiloid subfamily receptor 1 (TRPV1, previously known as VR1) to determine if, similar to somatic afferents, this channel is required for development of hypersensitivity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS050758-04
Application #
7340140
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (04))
Program Officer
Porter, Linda L
Project Start
2005-01-15
Project End
2009-02-28
Budget Start
2007-12-01
Budget End
2009-02-28
Support Year
4
Fiscal Year
2008
Total Cost
$318,713
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Wang, Ting; Jing, Xiaotang; DeBerry, Jennifer J et al. (2013) Neurturin overexpression in skin enhances expression of TRPM8 in cutaneous sensory neurons and leads to behavioral sensitivity to cool and menthol. J Neurosci 33:2060-70
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Malin, Sacha; Molliver, Derek; Christianson, Julie A et al. (2011) TRPV1 and TRPA1 function and modulation are target tissue dependent. J Neurosci 31:10516-28

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