Chronic pain affects 100 million people in the United States at an annual cost surpassing $600 billion (2011 IOM report). Irritable bowel syndrome (IBS) and temporomandibular disorders (TMD) are functional chronic pain disorders of unknown etiology that are more prevalent in women, the pain fluctuates across the menstrual cycle, and the conditions are triggered/exacerbated by stress. The mechanisms underlying these conditions are not well understood so treatment options are poor. These conditions along with other functional pain syndromes overlap in presentation (>60% of TMD patients have IBS) further complicating pain management. A new experimental paradigm in rats models these comorbid pain conditions. Sub chronic stress induces transient visceral hypersensitivity that persists about 1 week. This new model of comorbid pain employs masseter muscle inflammation, modeling TMD, prior to the sub chronic stress to induce estrogen-dependent visceral hypersensitivity, modeling IBS. This comorbid visceral hypersensitivity persists months longer than the, transient visceral hypersensitivity induced by stress or masseter inflammation alone.
Three specific aims will examine peripheral and spinal mechanisms that contribute to the acute (2 days) and chronic (1 month) phases of the comorbid visceral hypersensitivity. It is hypothesized that as the effects of the stress component of the acute/transient visceral hypersensitivity recede, there is a shift from peripheral to spinal mechanisms to maintain the chronic comorbid visceral hypersensitivity.
Aim 1 will examine colonic afferent activity and the effects of peripheral CRF and mast cells in the acute and chronic phases.
Aim 2 will examine changes in spinal visceroceptive neuron activity during the transition from acute to chronic pain.
Aim 3 will test the hypothesis that unique gene signature sets, canonical and non-canonical signaling pathways and gene ontologies are enriched in anatomically relevant pain regions (colon, DRG, spinal cord) in the acute and chronic phases of comorbid visceral hypersensitivity. Successful completion of these specific aims will increase our understanding of mechanisms that contribute to the overlap of functional pain disorders, specifically TMD and IBS.

Public Health Relevance

Overlapping or comorbid functional pain syndromes are a serious pain management dilemma. In a new animal model designed to gain mechanistic understanding underlying these conditions, we will test the hypothesis that masseter muscle inflammation, modeling temporomandibular disorder, followed by a stress paradigm induces visceral hypersensitivity, modeling irritable bowel syndrome, which initially has peripheral and central components, but transitions to a central nervous system condition as the visceral hypersensitivity becomes chronic.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR015472-03
Application #
9276521
Study Section
Nursing and Related Clinical Sciences Study Section (NRCS)
Program Officer
Hamlet, Michelle R
Project Start
2015-08-04
Project End
2020-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Other Basic Sciences
Type
Schools of Dentistry/Oral Hygn
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201